Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contact Us Login 
An Official Publication of the Indian Association of Oral and Maxillofacial Pathologists

  Table of Contents    
Year : 2014  |  Volume : 18  |  Issue : 2  |  Page : 229-234

MicroRNAs - Biology and clinical applications

Department of Oral and Maxillofacial Pathology, Ragas Dental College and Hospital, Uthandi, Chennai, Tamil Nadu, India

Date of Submission21-Feb-2014
Date of Acceptance02-Jul-2014
Date of Web Publication17-Sep-2014

Correspondence Address:
Kannan Ranganathan
Department of Oral and Maxillofacial Pathology, Room no. 9, 2nd floor,2/102, East Coast Road, Uthandi, Chennai 600 119,Tamil Nadu
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-029X.140762

Rights and Permissions



MicroRNAs are a highly conserved group of small, non-coding RNA molecules, which are 19-25 nucleotides in size. Previously thought to be evolutionary debris with no evident function, these small RNAs have been found to control gene expression primarily by silencing the gene. MicroRNAs are critical to cell physiology and development. They are also implicated in pathological processes such as autoimmune diseases, viral infections and carcinogenesis.

Keywords: Gene silencing, MicroRNAs, non-coding RNAs

How to cite this article:
Ranganathan K, Sivasankar V. MicroRNAs - Biology and clinical applications. J Oral Maxillofac Pathol 2014;18:229-34

How to cite this URL:
Ranganathan K, Sivasankar V. MicroRNAs - Biology and clinical applications. J Oral Maxillofac Pathol [serial online] 2014 [cited 2023 Mar 20];18:229-34. Available from: https://www.jomfp.in/text.asp?2014/18/2/229/140762

   Introduction Top

Molecular biology's central dogma explains life using 3 macromolecules: Deoxyribonucleic acid (DNA)-the genetic material of almost all living organisms, -which is transcribed to Ribonucleic acid (RNA), which transmits genetic information from DNA to the cytoplasm to be translated to amino acids and forms protein which is a sequence of amino acids that forms the structural and functional basis of every cell. [1]

For decades, RNA was thought to play a very minor role in gene expression by converting genetic information from DNA into functional proteins upon receiving an appropriate signal. In the late 1960s, a subset of RNAs was found to control gene expression by stating which genes should turn on and which should turn off. [2] These non-coding RNAs, rightly named because they do not code for a protein, are of distinct classes distinguished based on their function and origin. These include  microRNA (miRNA), small temporal RNA (stRNA), short interfering RNA (siRNA), short hairpin RNA (shRNA), small nuclear RNAs (snRNA), small nucleolar RNAs (snoRNA), transfer RNAs (tRNA) and ribosomal RNAs (rRNA). [3]

MiRNAs and siRNAs are currently among the most studied small non-coding RNAs. Following completion of the Human Genome Project, it was found that there are about 1000 genes in humans that encode miRNAs, which account for approximately 3% of the human genome. [4],[5],[6] miRNAs are critical in determining cellular fate as they regulate development, maturation, differentiation and apoptosis of the cell, cell signaling, cellular interactions and homeostasis. Alternatively, they also assume central importance in our understanding of many pathologic conditions such as carcinogenesis. [7],[8] Small non-coding RNAs are thus at the forefront of modern biology, heralding in an era of RNomics (the study of small non-messenger RNA) and challenging a central dogma proposed by Francis Crick more than half a century ago.

   History Top

Living cells arose on Earth around 3.5 billion years ago when spontaneous reactions occurred between molecules of which RNA (Ribonucleic acid) molecules were the prime players. With time, protein catalysts accumulated, thereby resulting in the evolution of more complex and efficient cells and eventually the DNA double helix molecule, being more stable, replaced RNA in order to store the larger amounts of genetic information needed by these cells. The RNA molecule remained an intermediary, connecting the DNA, having the genetic function, with the proteins, having the catalytic function. [9]

Coding RNAs

Based on their function, RNA molecules can be broadly classified into coding RNAs and non-coding RNAs. Coding RNAs are molecules that code for a particular protein. They are key players in protein transcription and translation. The gene that codes for the protein of interest is unwound and transcribed into a single-stranded RNA molecule, the messenger RNA (mRNA), so called because it carries the genetic information from the nucleus into the cytoplasm, where it is translated into a sequence of amino acids forming a polypeptide chain. However, it remained unclear as to what made the genes to be transcribed into a particular protein and how the process was turned on and off in each cell. [1] Human genome analysis has revealed that a very small portion of the human genome is translated into functional proteins while the majority (approximately 65%) of the genome is transcribed into RNAs, whose function is still not determined. [10]

Non-coding RNAs

Non-coding RNAs, unlike mRNAs, do not encode protein but control various levels of gene expression. [11],[12] Based on their function, non-coding RNAs can be categorized into housekeeping RNAssuch as tRNAs, rRNAs, snRNAs and snoRNAs and regulatory RNAs. Housekeeping RNAs are usually constitutively expressed whereas regulatory non-coding RNAs are produced only at certain stages of cellular development and differentiation or in response to external stimuli. Among the small regulatory RNAs, miRNAs are the most phylogenetically conserved and function post-transcriptionally to regulate physiological processes by silencing the gene. [13],[14],[15]

Gene regulation

Genetic regulation is essential to development and is the process that controls the differentiation of a single totipotent cell into a functional, complex multicellular organism. An interspecies variation, or more simply, what makes us human, is not only the difference in the genetic makeup but also the differences in gene regulation. [16] It is also the cause of phenotypic variations among individuals of the same species as well as the reason for disease processes when the regulation is aberrant.

Both RNA and protein can be regulated to control the amount of active gene product formed by epigenetic control, chromatin remodeling through DNA modifications and regulating the transcript. This can occur at the transcriptional level, when the gene is transcribed to an RNA transcript; at the translational level, when the gene encodes a protein; or the post-transcription and post-translational level, after the gene product is synthesized. Small non-coding regulatory RNAs regulate post-transcriptional gene expression. [17]

Gene regulation can result in up-regulation or down-regulation of the gene product. Down-regulating the formation of active gene products or "turning off" the gene is called gene silencing. RNA interference (RNAi) is a method of sequence specific post-transcriptional gene silencing. [18] RNAi was first discovered in 1998 in Ceanorhabditiselegans and plays an important role in regulating eukaryotic gene expression, causing repression through various methods including mRNA degradation, inhibition of its translation or chromatin remodeling. [3],[18],[19]

RNAi (in mammals) and post-transcriptional gene silencing (PTGS) (in plants) has been thought to represent an evolutionarily conserved mechanism developed to protect against viruses and mobile genetic elements such as transposons, which causes genomic instability. [20],[21] Central to the mechanism of RNA interference are two small non-coding regulatory RNAs-miRNAs and small interfering RNAs.

   The mirna and sirna gene family Top

miRNAs are highly conserved class of small (19-25 nucleotides), non-coding RNAs, which regulate post-transcriptional gene expression by binding to target mRNAs and result in gene silencing. [22],[23] In the genome, miRNAs can be found situated in the exons of non-coding genes, introns of coding and non-coding genes and the intragenic regions. [24] Small interfering RNAs (siRNAs) are approximately 22 nucleotides in length and mediate RNA interference (RNAi). Both miRNAs and siRNAs mediate the down-regulation of gene expression; however, their biogenesis and method of gene silencing differs significantly.[25],[26]

The first miRNA, lin-4 (abnormal cell LINeage) was discovered by Ambros and coworkers (1993) in C. elegans as an endogenous regulator of genes that regulate developmental timing. [10] The second miRNA, let-7 (LEThal), was discovered 7 years later and found to function similar to lin-4. Eventually, two categories of small RNAs were established that regulated gene expression: miRNAs, which regulate endogenous genes and siRNAs, which defend genome integrity in response to foreign or invasive nucleic acids such as viruses, transgenes and transposons. [27],[28]

Following the discovery of lin-4 and let-7, several hundreds of miRNAs have been identified. Some miRNAs, such as let-7, are highly conserved through evolution and are essential to many biological processes, while the individuality of an organism can be ascribed to lineage- and species-specific miRNAs. [29],[30] There are currently 1872 precursor and 2578 mature human miRNA sequences listed in the miRNA registry (Sanger miRBase release 20; http://www.mirbase.org/). Almost 60% of mammalian mRNAs are predicted targets of a relatively small number of miRNAs, suggesting that a given miRNA can silence many target genes. This is thought to be because miRNA does not require perfect sequence complementarity with its target mRNA. [31]

   Biogenesis Of MIRNAs Top

miRNAs are produced through transcription of miRNA genes in the nucleus known as miRNAs precursor genes (mir-gene). The miRNA transcripts are then spliced and capped similar to protein coding mRNA transcripts. These primary miRNAs form a hairpin-shaped stem loop, prior to being processed into pre-miRNAs. This processing is carried out by a microprocessor complex that consists of Drosha (RNase III endonuclease) and DiGeorge syndrome critical region 8 (DGCR8) or Pasha, which is an essential cofactor. This complex processes the primary mircoRNAs into pre-miRNAs, which are 60- to 70-nucleotide long and contain a 5′ phosphate and a 3′ nucleotide overhang. The pre-miRNA is then transported to the cytoplasm by exportin 5 of the Ran transport receptor family. [3],[32]

In the cytoplasm, the pre-miRNA is further processed to a short double strand miRNA by partner proteins Dicer (second RNase III endonuclease) and trans-activator RNA binding protein (TRBP). The duplex is then unwound by a helicase and the final mature miRNA is generated. Dicer also initiates the formation of the RNA-induced silencing complex (RISC). The mature miRNA product is a single-stranded, non-coding, regulatory RNA molecule 22 nucleotides long, which is guided to the target mRNA after it is incorporated into an RNA-induced silencing complex (RISC). [33]

The Argonaute (Ago) family of proteins is a major component of RISC and functions as a protector, protecting the RISC-loaded mature miRNA from degradation. After its function is complete, however, the mature miRNA is degraded. [34]

miRNAs have also been shown to be produced by two Drosha independent, non-canonical or alternative pathways. In the first pathway, early processing is carried out by spliceosome and a debranching enzyme to produce the short hairpin structure. These miRNAs have been called mirtrons. In the other non-canonical pathway, short hairpin RNAs (shRNAs) undergo processing by unknown nucleases into pre-miRNAs, which then follow the regular sequence of being processed into miRNAs by Dicer. These miRNAs are therefore called shRNA-derived miRNAs. [35]

The level of complementarities between the target mRNA and miRNA determines the method of binding and silencing. [36] miRNAs and siRNAs involved in RNAi use the same RISC to direct silencing. After that, the mechanism diverges-miRNAs attach imperfectly to mRNA and form a bulge that prevent mRNA from producing protein while siRNA binds perfectly with the target mRNA and destroy the mRNA. [3]

   Role in physiology Top

miRNAs have been found to regulate almost all cellular functions including cell proliferation, growth, differentiation and apoptosis. They are thought to play a role in specifying tissue identity since they are involved in the process of differentiation into specific tissue. Thus, the expression of miRNA in a specific cell type can be a useful marker for identifying the particular cell type. [37]

Tooth development

Specific codes of miRNAs have been identified which regulate cell differentiation and are required for tooth patterning; size, shape and number determination. [38]

Stem cells and miRNAs

miRNAs have been implicated in controlling the fate and behavior of stem cells. Down-regulation of miR-21, targets Nanog, SOX2 and OCT4, which are essential for stem cell self-renewal. Self-renewal is also promoted by the miR-290-295 cluster, which epigenetically silences OCT4. Embryonic stem cell differentiation is promoted by miR-296 and inhibited by miR-22. [39]

Stem cells divide to produce an undifferentiated stem cell and a daughter cell that may differentiate. This division is a carefully regulated process since excess divisions may result in cancer while too few divisions may lead to a loss of tissue homeostasis. [40] miR-138 has been found to negatively regulate osteogenic differentiation of human Mesenchymal Stem Cells (hMSCs). Thus, to increase bone formation in vivo, osteogenic differentiation of hMSCs can be accelerated by inhibiting miR-138. Another miRNA, miR-125b, has been shown to inhibit osteoblastic differentiation. The miRNA, miR-26a modulates osteogenic differentiation of stem cells derived from human adipose tissue by targeting the SMAD1 transcription factor. [39],[41]

Induced pluripotent stem (iPS) cells were first created by introducing reprogramming factors (So×2, Oct3/4, c-Myc and Klf4) into fibroblasts. The factor, c-Myc represses miRNAs, such as let-7a, miR-21 and miR-29a, during reprogramming. Cell types from different tissues are capable of being reprogrammed to iPS cells but the reprogramming efficacy is very low (0.01-0.2%). It has been found that miR-93 and miR-106b enhance reprogramming efficacy. [42]

   Role in pathology Top

The involvement of miRNAs in human diseases was identified from two observations. The first was that humans with mutations in fragile (a RISC cofactor) or DGCR8 (a Drosha cofactor) suffer from mental retardation and DiGeorge syndrome, respectively. Second, almost 50% of human miRNA genes are present at genetic loci which are implicated in cancers. [33]

MiRNA and cancer

In humans, the balance between apoptosis and proliferation is vital for homeostasis maintenance. Some miRNAs are oncogenes (oncomiRs) and some are tumor suppressor miRNAs. miRNAs play a vital role in evaluating the development, progression, prognosis, diagnosis and treatment response in cancer patients. [37]

miRNAs target apoptotic genes, thereby mediating tumorigenesis. The capability of cancer stem cells to evade the G1/S checkpoint is partly due to miRNAs. Calin et al. reported a unique pattern of miRNA expression signatures that were capable of differentiating aggressive from indolent chronic lymphocytic leukemia (CLL). [43]

Recent evidence indicates that miRNAs play an important role in p53 tumor suppressor pathways. He et al. found miR-34a, miR-34b and miR-34c to be closely linked to p53 status and oncogenic stress and DNA damage induced their expression. [44],[45]

Oral cancer

miRNA profiling in head and neck squamous cell carcinomas (HNSCCs) revealed miR-451 to be a potential prognostic marker. miR-375 and miR-106b-25 cluster to be mediate the development and progression of HNSCC. [46] Kozaki et al. showed that miR-137 and miR-193a function as tumor suppressors and are silenced in oral carcinogenesis. [47] Wong et al. studied the expression patterns of miRNAs in squamous cell carcinoma of the tongue and found an over expression of miR-184 which was thought to have an oncogenic role by inducing proliferative and anti-apoptotic processes. [48],[49]

Henson et al. found that the development and/or progression of oral squamous cell carcinoma are associated with the down-regulation of miR-100 and miR-125b and these miRNAs may be the reason for the low sensitivity to ionizing radiation. [50] Li et al. found that miR-21 was an independent prognostic indicator for tongue squamous cell carcinoma and played a role in its development by inhibiting apoptosis of cancer cells. [51]

Metastasis is a significant event in the progression of HNSCC and Liu et al. found miR-138 to acts as a tumor suppressor which could be a potential target for therapy in patients with a risk of metastasis. [52]

Cervigne et al. found miRNA signatures that could potentially identify leukoplakias which are at a risk of malignant transformation. The expression of miR-21, miR-181b and miR-345 were found to be consistently increased and associated with increase in the severity of the lesion. Overexpression of these miRNAs was thought to play a major role in malignant transformation. [53]

miRNAs and viruses

RNA interference and gene silencing is an innate host cell mechanism to protect against viruses. Viruses, on the other hand, have evolved to bypass host interference by various mechanisms which include altering miRNA expression in the host cell in a way that promotes viral replication. Nef and rev are viral genes in the human immunodeficiency virus that suppress host silencing mechanisms. [54],[55],[56]

miRNAs in autoimmune diseases

miRNAs are found to regulate immune response, immune cell development and prevention of autoimmunity. A possible role has been suggested for miRNA in the development of autoimmune diseases such as Rheumatoid Arthritis (RA), Sjφgren'ssyndrome and Systemic Lupus Erythematosus (SLE). Distinctive miRNA expression patterns have been linked to salivary gland dysfunction in patients with Sjφgren's syndrome and these miRNAs can serve as potential biomarkers for the disease. Proteins such as Ago2, involved in the biogenesis of miRNAs, have been found to be targets of these autoantibodies. [57],[58]

Periodontal disease

miRNAs have been shown to play a major role in regulating the immuno-inflammatory response. Xie et al. compared the miRNA profiles of inflamed and healthy gingival tissue and found 91 miRNAs up-regulated and 34miRNAs down-regulated in the inflamed gingival tissue indicating a plausible relationship between periodontal inflammation and miRNAs. miRNAs may be involved in regulating toll-like receptors (TLRs) in periodontal inflammation. [59]

   The Clinical Potential of Mirnas: Diagnostic, Prognostic and Therapeutic Implications Top

The majority of miRNA are intracellular, but some miRNA exists in the extracellular compartment and are seen to be mediators of cell-cell communication. Extracellular miRNAs can be isolated from body fluids such as serum, plasma and saliva. They can act as potential biomarkers for the detection of various diseases. [60] Salivary miRNAs can be used clinically to detect oral cancer. Healthy saliva contains approximately 50 miRNAs. Two miRNAs in particular, miR-125a and miR-200a have been found exclusively in the saliva of oral cancer patients and are diagnostic markers of the disease. [61],[62],[63]

The presence of RNAases in body fluids precludes the existence of any intact RNA. Thus, it has been theorized and proven that miRNA exist extracellularly within small, cell-secreted vesicles called "exosomes". [64] These vesicles can regulate intercellular communication and facilitate certain processes such as antigen presentation. Exosomes are present in body fluids that include plasma, blood, breast milk, saliva and urine and can have a potential role in immunotherapy and vaccination modalities and as a potential vector for gene therapy. Salivary exosomal miRNAs may be important not only as a diagnostic tool but can also provide information regarding the role of miRNAs in the pathophysiology of various salivary gland diseases. [64]

   Quantification Top

Microarrays and quantitative PCR (qPCR)-based methods are the major modalities used to profile miRNAs. Quantitative PCR methods are widely available, relatively inexpensive and allow for the measurements of minute quantities of miRNAs. However, the primer design can influence the results. With microarray-based methods, it is difficult to detect different miRNAs at one time. Northern blotting, direct sequencing and ligation-based measurement can also be used. [62]In situ hybridization is a reliable method to localize and detect miRNAs in both frozen tissue and paraffin-embedded sections. To confirm the function of a specific miRNA, loss-of-function and gain-of-function approaches can be applied in vivo in mammals as well as in vitro in cultured cells. [37]

   Acknowledgements Top

Department of Oral and Maxillofacial Pathology, Ragas Dental College and Hospitals.

   References Top

1.Lodish HB, Zipursky SL, et al. Molecular Cell Biology. 4 th ed. New York: W H Freeman; 2000.  Back to cited text no. 1
2.Condorelli G, Dimmeler S. MicroRNAs: Components of an integrated system controlling cardiac development, physiology, and disease pathogenesis. CardiovascRes 2008;79:551-2.  Back to cited text no. 2
3.Bahadori M. New Advances in RNAs. ArchIranMed 2008;11:435-43.  Back to cited text no. 3
4.Mattick JS, Makunin IV. Small regulatory RNAs in mammals. HumMolecular Genet 2005;14:R121-32.  Back to cited text no. 4
5.Kim VN, Nam JW. Genomics of microRNA. Trends Genet 2006;22:165-73.  Back to cited text no. 5
6.Saini HK, Griffiths-Jones S, Enright AJ. Genomic analysis of human microRNA transcripts. ProcNatl AcadSci U S A 2007;104:17719-24.  Back to cited text no. 6
7.Schickel R, Boyerinas B, Park SM, Peter ME. MicroRNAs: Key players in the immune system, differentiation, tumorigenesis and cell death. Oncogene 2008;27:5959-74.  Back to cited text no. 7
8.Zhang W, Dahlberg JE, Tam W. MicroRNAs in tumorigenesis: A primer. Am J Pathol 2007;171:728-38.  Back to cited text no. 8
9.Alberts BB, Lewis J, et al. Molecular Biology of the Cell. 3 rd ed. New York: Garland Science; 1994.  Back to cited text no. 9
10.Mattick JS, Makunin IV. Non-coding RNA. HumMolGenet 2006;15 Spec No 1:R17-29.  Back to cited text no. 10
11.Ambros V. microRNAs: Tiny Regulators with Great Potential. Cell 2001;107:823-6.  Back to cited text no. 11
12.Erdmann VA, Barciszewska MZ, Szymanski M, Hochberg A, de Groot N, Barciszewski J. The non-coding RNAs as riboregulators. Nucleic Acids Res 2001;29:189-93.  Back to cited text no. 12
13.Szymanski M, Barciszewski J. Beyond the proteome: Non-coding regulatory RNAs. Genome Biol 2002;3:reviews0005.  Back to cited text no. 13
14.Szymanski M, Erdmann VA, Barciszewski J. Noncoding regulatory RNAs database. Nucleic Acids Res 2003;31:429-31.  Back to cited text no. 14
15.Zhao Y, Srivastava D. A developmental view of microRNA function. Trends BiochemSci 2007;32:189-97.  Back to cited text no. 15
16.Strachan T, Read AP. Human molecular genetics. 1 st ed. New York: Wiley-Liss Bios Scientific Publishers, an imprint of Taylor and Francis Group; 1999.  Back to cited text no. 16
17.Chen K, Rajewsky N. The evolution of gene regulation by transcription factors and microRNAs. Nat Rev Genet 2007;8:93-103.  Back to cited text no. 17
18.Hannon GJ. RNA interference. Nature 2002;418:244-51.  Back to cited text no. 18
19.Valencia-Sanchez MA, Liu J, Hannon GJ, Parker R. Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Develop 2006;20:515-24.  Back to cited text no. 19
20.Hammond SM, Caudy AA, Hannon GJ. Post-transcriptional gene silencing by double-stranded RNA. NatRev Genet 2001;2:110-9.  Back to cited text no. 20
21.Scherr M, Eder M. Gene silencing by small regulatory RNAs in mammalian cells. Cell Cycle 2007;6:444-9.  Back to cited text no. 21
22.Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: Are the answers in sight? NatRevGenet 2008;9:102-14.  Back to cited text no. 22
23.Garofalo M, Croce CM. microRNAs: Master regulators as potential therapeutics in cancer. Annu Rev Pharmacol Toxicol 2011;51:25-43.  Back to cited text no. 23
24.Shukla GC, Singh J, Barik S. MicroRNAs: Processing, maturation, target recognition and regulatory functions. MolCellPharmacol 2011;3:83-92.  Back to cited text no. 24
25.Cheng JC, Moore TB, Sakamoto KM. RNA interference and human disease. MolGenetMetab 2003;80:121-8.  Back to cited text no. 25
26.Macfarlane LA, Murphy PR. MicroRNA: Biogenesis, function and role in cancer. CurrGenomics 2010;11:537-61.  Back to cited text no. 26
27.Carthew RW, Sontheimer EJ. Origins and Mechanisms of miRNAs and siRNAs. Cell. 2009;136:642-55.  Back to cited text no. 27
28.Zamore PD, Haley B. Ribo-gnome: The big world of small RNAs. Science 2005;309:1519-24.  Back to cited text no. 28
29.Kolokythas A, Miloro M, Zhou X. Review of microRNA deregulation in oral cancer. Part I. J Oral MaxillofacRes2011;2:e1.  Back to cited text no. 29
30.De Mulder K, Berezikov E. Tracing the evolution of tissue identity with microRNAs. Genome Biol 2010;11:111.  Back to cited text no. 30
31.Friedman RC, Farh KK, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 2009;19:92-105.  Back to cited text no. 31
32.Shivdasani RA. MicroRNAs: Regulators of gene expression and cell differentiation. Blood 2006;108:3646-53.  Back to cited text no. 32
33.Berkhout B, Jeang KT. RISCy business: MicroRNAs, pathogenesis, and viruses. J BiolChem 2007;282:26641-5.  Back to cited text no. 33
34.He L, Hannon GJ. MicroRNAs: Small RNAs with a big role in gene regulation. NatRev Genet 2004;5:522-31.  Back to cited text no. 34
35.Pushparaj PN, Aarthi JJ, Manikandan J, Kumar SD. siRNA, miRNA, and shRNA: In vivo applications. J DentRes 2008;87:992-1003.  Back to cited text no. 35
36.Gu S, Kay MA. How do miRNAs mediate translational repression? Silence 2010;1:11.  Back to cited text no. 36
37.Zhang C. MicroRNomics: A newly emerging approach for disease biology. PhysiolGenomics 2008;33:139-47.  Back to cited text no. 37
38.Cao H, Wang J, Li X, Florez S, Huang Z, Venugopalan SR, et al. MicroRNAs play a critical role in tooth development. JDentRes 2010;89:779-84.  Back to cited text no. 38
39.Gangaraju VK, Lin H. MicroRNAs: Key regulators of stem cells. NatRev MolCell Biol 2009;10:116-25.  Back to cited text no. 39
40.Hatfield S, Ruohola-Baker H. microRNA and stem cell function. Cell Tissue Res 2008;331:57-66.  Back to cited text no. 40
41.Eskildsen T, Taipaleenmaki H, Stenvang J, Abdallah BM, Ditzel N, Nossent AY, et al. MicroRNA-138 regulates osteogenic differentiation of human stromal (mesenchymal) stem cells in vivo. Proc Natl Acad Sci U S A 2011;108:6139-44.  Back to cited text no. 41
42.Yang CS, Li Z, Rana TM. microRNAs modulate iPS cell generation. RNA 2011;17:1451-60.  Back to cited text no. 42
43.Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, et al. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl JMed 2005;353:1793-801.  Back to cited text no. 43
44.Feng Z, Zhang C, Wu R, Hu W. Tumor suppressor p53 meets microRNAs. JMolCell Biol 2011;3:44-50.  Back to cited text no. 44
45.He L, He X, Lim LP, de Stanchina E, Xuan Z, Liang Y, et al. A microRNA component of the p53 tumour suppressor network. Nature 2007;447:1130-4.  Back to cited text no. 45
46.Hui AB, Lenarduzzi M, Krushel T, Waldron L, Pintilie M, Shi W, et al. Comprehensive MicroRNA profiling for head and neck squamous cell carcinomas. Clin Cancer Res 2010;16:1129-39.  Back to cited text no. 46
47.Kozaki K, Imoto I, Mogi S, Omura K, Inazawa J. Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in oral cancer. Cancer Res 2008;68:2094-105.  Back to cited text no. 47
48.Chen LH, Tsai KL, Chen YW, Yu CC, Chang KW, Chiou SH, et al. MicroRNA as a novel modulator in head and neck squamous carcinoma. JOncol 2010;2010:135632.  Back to cited text no. 48
49.Wong TS, Liu XB, Wong BY, Ng RW, Yuen AP, Wei WI. Mature miR-184 as potential oncogenic microRNA of squamous cell carcinoma of tongue. ClinCancer Res 2008;14:2588-92.  Back to cited text no. 49
50.Henson BJ, Bhattacharjee S, O'Dee DM, Feingold E, Gollin SM. Decreased expression of miR-125b and miR-100 in oral cancer cells contributes to malignancy. GenesChromosomes Cancer 2009;48:569-82.  Back to cited text no. 50
51.Li J, Huang H, Sun L, Yang M, Pan C, Chen W, et al. MiR-21 indicates poor prognosis in tongue squamous cell carcinomas as an apoptosis inhibitor. ClinCancer Res2009;15:3998-4008.  Back to cited text no. 51
52.Liu X, Jiang L, Wang A, Yu J, Shi F, Zhou X. MicroRNA-138 suppresses invasion and promotes apoptosis in head and neck squamous cell carcinoma cell lines. Cancer Lett 2009;286:217-22.  Back to cited text no. 52
53.Cervigne NK, Reis PP, Machado J, Sadikovic B, Bradley G, Galloni NN, et al. Identification of a microRNA signature associated with progression of leukoplakia to oral carcinoma. Hum MolGenet 2009;18:4818-29.  Back to cited text no. 53
54.Yeung ML, Bennasser Y, Myers TG, Jiang G, Benkirane M, Jeang KT. Changes in microRNA expression profiles in HIV-1-transfected human cells. Retrovirology 2005;2:81.  Back to cited text no. 54
55.Ouellet DL, Plante I, Barat C, Tremblay MJ, Provost P. Emergence of a complex relationship between HIV-1 and the microRNA pathway. Methods Mol Biol 2009;487:415-33.  Back to cited text no. 55
56.Westerhout EM, Ooms M, Vink M, Das AT, Berkhout B. HIV-1 can escape from RNA interference by evolving an alternative structure in its RNA genome. Nucleic Acids Res 2005;33:796-804.  Back to cited text no. 56
57.Pauley KM, Cha S, Chan EK. MicroRNA in autoimmunity and autoimmune diseases. J Autoimmun 2009;32:189-94.  Back to cited text no. 57
58.Alevizos I, Alexander S, Turner RJ, Illei GG. MicroRNA expression profiles as biomarkers of minor salivary gland inflammation and dysfunction in Sjogren's syndrome. Arthritis Rheum 2011;63:535-44.  Back to cited text no. 58
59.Xie YF, Shu R, Jiang SY, Liu DL, Zhang XL. Comparison of microRNA profiles of human periodontal diseased and healthy gingival tissues. Int J Oral Sci 2011;3:125-34.  Back to cited text no. 59
60.Kosaka N, Iguchi H, Ochiya T. Circulating microRNA in body fluid: A new potential biomarker for cancer diagnosis and prognosis. Cancer Sci 2010;101:2087-92.  Back to cited text no. 60
61.Kosaka N, Izumi H, Sekine K, Ochiya T. microRNA as a new immune-regulatory agent in breast milk. Silence 2010;1:7.  Back to cited text no. 61
62.Etheridge A, Lee I, Hood L, Galas D, Wang K. Extracellular microRNA: A new source of biomarkers. MutatRes 2011;717:85-90.  Back to cited text no. 62
63.Park NJ, Zhou H, Elashoff D, Henson BS, Kastratovic DA, Abemayor E, et al. Salivary microRNA: Discovery, characterization, and clinical utility for oral cancer detection. ClinCancer Res 2009;15:5473-7.  Back to cited text no. 63
64.Michael A, Bajracharya SD, Yuen PS, Zhou H, Star RA, Illei GG, et al. Exosomes from human saliva as a source of microRNA biomarkers. Oral Dis 2010;16:34-8.  Back to cited text no. 64

This article has been cited by
1 HCV eradication with DAAs differently affects HIV males and females: A whole miRNA sequencing characterization
Daniel Valle-Millares, Óscar Brochado-Kith, Alicia Gómez-Sanz, Luz Martín-Carbonero, Pablo Ryan, Ignacio De los Santos, Juan M. Castro, Jesús Troya, Mario Mayoral-Muńoz, Guillermo Cuevas, Paula Martínez-Román, Jesús Sanz-Sanz, María Muńoz-Muńoz, María Á Jiménez-Sousa, Salvador Resino, Verónica Briz, Amanda Fernández-Rodríguez
Biomedicine & Pharmacotherapy. 2022; 145: 112405
[Pubmed] | [DOI]
2 Gastrointestinal disorder biomarkers
Reza Ranjbar, Mohamad Ghasemian, Mahmood Maniati, Seyyed Hossein Khatami, Navid Jamali, Mortaza Taheri-Anganeh
Clinica Chimica Acta. 2022;
[Pubmed] | [DOI]
3 Delivery of therapeutic miRNAs using nanoscale zeolitic imidazolate framework for accelerating vascularized bone regeneration
Hao Feng, Ziyu Li, Wenjia Xie, Qianbing Wan, Yongwen Guo, Junyu Chen, Jian Wang, Xibo Pei
Chemical Engineering Journal. 2022; 430: 132867
[Pubmed] | [DOI]
4 microRNAs in the blastocoel fluid as accessible indicators of chromosomal normality
Masoumeh Esmaeilivand, Amir Fattahi, Ali Abedelahi, Kobra Hamdi, Laya Farzadi, Sepide Goharitaban, Behrooz Niknafs
Reproductive Biology. 2022; 22(4): 100695
[Pubmed] | [DOI]
5 Adipocyte differentiation between obese and lean conditions depends on changes in miRNA expression
Yerim Heo, Hyunjung Kim, Jiwon Lim, Sun Shim Choi
Scientific Reports. 2022; 12(1)
[Pubmed] | [DOI]
6 Circular RNA profiles of osteoarthritic synovium
Pengjuan Liu, Ge Gao, Xiao Zhou, Xiao Zhang, Qiaoling Cai, Zhongyuan Xiang, Xiongjie Shen, Xiang Wu
Molecular Omics. 2022;
[Pubmed] | [DOI]
7 MiR-137-mediated negative relationship between LGR4 and RANKL modulated osteogenic differentiation of human adipose-derived mesenchymal stem cells
Cong Fan, Yulong Li
Genetics and Molecular Biology. 2022; 45(3)
[Pubmed] | [DOI]
8 Role of miRNA polymorphism in recurrent pregnancy loss: a systematic review and meta-analysis
Priyanka Srivastava, Chitra Bamba, Seema Chopra, Kausik Mandal
Biomarkers in Medicine. 2022;
[Pubmed] | [DOI]
9 Epigenome Modulation Induced by Ketogenic Diets
Paola Ungaro, Immacolata Cristina Nettore, Fabiana Franchini, Giuseppe Palatucci, Giovanna Muscogiuri, Annamaria Colao, Paolo Emidio Macchia
Nutrients. 2022; 14(15): 3245
[Pubmed] | [DOI]
10 The clinical significance of circulating miR-21, miR-142, miR-143, and miR-146a in patients with prostate cancer
Ibrahim Bolayirli, Bülent Önal, Mutlu Adigüzel, Dildar Konukoglu, Çetin Demirdag, Eda Kurtulus, Fethi Türegün, Hafize Uzun
Journal of Medical Biochemistry. 2022; 41(2): 191
[Pubmed] | [DOI]
11 Modulation of Cellular MicroRNA by HIV-1 in Burkitt Lymphoma Cells—A Pathway to Promoting Oncogenesis
Beatrice Relebogile Ramorola, Taahira Goolam-Hoosen, Leonardo Alves de Souza Rios, Shaheen Mowla
Genes. 2021; 12(9): 1302
[Pubmed] | [DOI]
12 Preclinical Imaging Evaluation of miRNAs’ Delivery and Effects in Breast Cancer Mouse Models: A Systematic Review
Francesca Maria Orlandella, Luigi Auletta, Adelaide Greco, Antonella Zannetti, Giuliana Salvatore
Cancers. 2021; 13(23): 6020
[Pubmed] | [DOI]
13 Adipocyte, Immune Cells, and miRNA Crosstalk: A Novel Regulator of Metabolic Dysfunction and Obesity
Sonia Kiran, Vijay Kumar, Santosh Kumar, Robert L Price, Udai P. Singh
Cells. 2021; 10(5): 1004
[Pubmed] | [DOI]
14 Novel approaches on identification of conserved miRNAs for broad-spectrum Potyvirus control measures
Ramamoorthy Sankaranarayanan, Sankara Naynar Palani, Nagarajan Tamilmaran, A. S. Punitha Selvakumar, P. Chandra Sekar, Jebasingh Tennyson
Molecular Biology Reports. 2021; 48(3): 2377
[Pubmed] | [DOI]
15 miR-124 ameliorates dopaminergic neurons loss, reduces oxidative stress via targeting Axin1 and activating Wnt/ß-catenin signaling in Parkinson's disease mice
Fubo Zhang, Yufang Yao, Na Miao, Nan Wang, Xin Xu, Chaoping Yang
Archives of Gerontology and Geriatrics. 2021; : 104588
[Pubmed] | [DOI]
16 The pleiotropic neuroprotective effects of resveratrol in cognitive decline and Alzheimer’s disease pathology: From antioxidant to epigenetic therapy
Christian Grińán-Ferré, Aina Bellver-Sanchis, Vanessa Izquierdo, Rubén Corpas, Joan Roig-Soriano, Miguel Chillón, Cristina Andres-Lacueva, Milán Somogyvári, Csaba Soti, Coral Sanfeliu, Mercč Pallŕs
Ageing Research Reviews. 2021; 67: 101271
[Pubmed] | [DOI]
17 Dissecting the role of micro-RNAs as a diagnostic marker for polycystic ovary syndrome: a systematic review and meta-analysis
Ritu Deswal, Amita Suneja Dang
Fertility and Sterility. 2020; 113(3): 661
[Pubmed] | [DOI]
18 A concise review on impacts of microRNAs in biology and medicine of hepatitis C virus
Mohammad Moradi, Farzad Mozafari, Shirin Hosseini, Rouhullah Rafiee, Faezeh Ghasemi
Gene Reports. 2020; 20: 100761
[Pubmed] | [DOI]
19 Crosstalk among colon cancer-derived exosomes, fibroblast-derived exosomes, and macrophage phenotypes in colon cancer metastasis
Meiyun Wang, Zhaoliang Su, Prince Amoah Barnie
International Immunopharmacology. 2020; 81: 106298
[Pubmed] | [DOI]
20 Analysis of microRNA-34a expression profile and rs2666433 variant in colorectal cancer: a pilot study
Manal S. Fawzy, Afaf T. Ibrahiem, Baraah T. Abu AlSel, Saleh A. Alghamdi, Eman A. Toraih
Scientific Reports. 2020; 10(1)
[Pubmed] | [DOI]
21 miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis
Carmen Elena Condrat, Dana Claudia Thompson, Madalina Gabriela Barbu, Oana Larisa Bugnar, Andreea Boboc, Dragos Cretoiu, Nicolae Suciu, Sanda Maria Cretoiu, Silviu Cristian Voinea
Cells. 2020; 9(2): 276
[Pubmed] | [DOI]
22 Identification and Differential Expression of microRNA in Response to Elevated Phospholipase C? Expression in Liver RH 35 Carcinoma Cells
Xiaoguang Chen, Xuemin Zhu, Zhiguo Wei, Qiongxia Lv
Cytology and Genetics. 2020; 54(6): 555
[Pubmed] | [DOI]
23 Transcriptional Regulation of Channelopathies in Genetic and Acquired Epilepsies
Karen M. J. van Loo, Albert J. Becker
Frontiers in Cellular Neuroscience. 2020; 13
[Pubmed] | [DOI]
24 Role and Mechanisms of RAGE-Ligand Complexes and RAGE-Inhibitors in Cancer Progression
Ali H. El-Far, Grazyna Sroga, Soad K. Al Jaouni, Shaker A. Mousa
International Journal of Molecular Sciences. 2020; 21(10): 3613
[Pubmed] | [DOI]
25 miR-146b Functions as an Oncogene in Oral Squamous Cell Carcinoma by Targeting HBP1
Kui Li, Zheng Zhou, Ju Li, Rui Xiang
Technology in Cancer Research & Treatment. 2020; 19: 1533033820
[Pubmed] | [DOI]
26 Identification of genes and miRNA associated with idiopathic recurrent pregnancy loss: an exploratory data mining study
Wael Bahia, Ismael Soltani, Anouar Abidi, Anis Haddad, Salima Ferchichi, Samia Menif, Wassim Y. Almawi
BMC Medical Genomics. 2020; 13(1)
[Pubmed] | [DOI]
27 Analysis of miRNAs and their target genes associated with mucosal damage caused by transport stress in the mallard duck intestine
Hao Zhang, Fang Chen, Zhenhua Liang, Yan Wu, Jinsong Pi, Lixia Wang, Jinping Du, Jie Shen, Ailuan Pan, Yuejin Pu, José Carlos M. Mombach
PLOS ONE. 2020; 15(8): e0237699
[Pubmed] | [DOI]
28 MicroRNA-451b participates in coronary heart disease by targeting VEGFA
Jie Lin, Jun Jiang, Ruifang Zhou, Xiaojie Li, Jun Ye
Open Medicine. 2019; 15(1): 1
[Pubmed] | [DOI]
29 miRNA-103 promotes chondrocyte apoptosis by down-regulation of Sphingosine kinase-1 and ameliorates PI3K/AKT pathway in osteoarthritis
Fang Li, Jianhua Yao, Qingqing Hao, Zheping Duan
Bioscience Reports. 2019; 39(10)
[Pubmed] | [DOI]
30 miRNA analysis with Prost! reveals evolutionary conservation of organ-enriched expression and post-transcriptional modifications in three-spined stickleback and zebrafish
Thomas Desvignes, Peter Batzel, Jason Sydes, B. Frank Eames, John H. Postlethwait
Scientific Reports. 2019; 9(1)
[Pubmed] | [DOI]
31 Integrated network analysis identifies hsa-miR-4756-3p as a regulator of FOXM1 in Triple Negative Breast Cancer
Yuanliang Gu, Wenjuan Wang, Xuyao Wang, Hongyi Xie, Xiaojuan Ye, Peng Shu
Scientific Reports. 2019; 9(1)
[Pubmed] | [DOI]
32 MicroRNA-146a inhibits NF-?B activation and pro-inflammatory cytokine production by regulating IRAK1 expression in THP-1 cells
Chunlei Zhou, Lan Zhao, Kai Wang, Qianru Qi, Meng Wang, Lei Yang, Ping Sun, Hong Mu
Experimental and Therapeutic Medicine. 2019;
[Pubmed] | [DOI]
33 ?icroRNA-221 participates in cerebral ischemic stroke by modulating endothelial cell function by regulating the PTEN/PI3K/AKT pathway
Han Peng, Hua Yang, Xin Xiang, Shenggang Li
Experimental and Therapeutic Medicine. 2019;
[Pubmed] | [DOI]
34 Identification and functional analysis of microRNAs in rats following focal cerebral ischemia injury
Xianchun Duan, Jianghua Gan, Dai-Yin Peng, Qiuyu Bao, Ling Xiao, Liangbing Wei, Jian Wu
Molecular Medicine Reports. 2019;
[Pubmed] | [DOI]
35 MicroRNA-148b inhibits proliferation and the epithelial-mesenchymal transition and increases radiosensitivity in non-small cell lung carcinomas by regulating ROCK1
Haitao Luo, Caixia Liang
Experimental and Therapeutic Medicine. 2018;
[Pubmed] | [DOI]
36 miR-98-5p promotes osteoblast differentiation in MC3T3-E1 cells by targeting CKIP-1
Qiliang Liu, Yong Guo, Yang Wang, Xianqiong Zou, Zhixiong Yan
Molecular Medicine Reports. 2018;
[Pubmed] | [DOI]
37 Micro RNA-4651 Serves as a Potential Biomarker for Prognosis When Selecting Hepatocellular Carcinoma Patients for Postoperative Adjuvant Transarterial Chemoembolization Therapy
Tian-Qi Zhang, Qun-Qing Su, Xiao-Ying Huang, Jin-Guang Yao, Chao Wang, Qiang Xia, Xi-Dai Long, Yun Ma
Hepatology Communications. 2018; 2(10): 1259
[Pubmed] | [DOI]
38 Decreased MicroRNA miR-181c Expression Associated with Gastric Cancer
Luanna Munhoz Zabaglia, Nicole Chiuso Bartolomeu, Mônica Pezenatto dos Santos, Rita Luiza Peruquetti, Elizabeth Chen, Marilia de Arruda Cardoso Smith, Spencer Luiz Marques Payăo, Lucas Trevizani Rasmussen
Journal of Gastrointestinal Cancer. 2018; 49(1): 97
[Pubmed] | [DOI]
39 Diagnostic and prognostic potential of serum microRNA-4651 for patients with hepatocellular carcinoma related to aflatoxin B1
Xue-Min Wu, Zhi-Feng Xi, Pinhu Liao, Hong-Dong Huang, Xiao-Ying Huang, Chao Wang, Yun Ma, Qiang Xia, Jin-Guang Yao, Xi-Dai Long
Oncotarget. 2017; 8(46): 81235
[Pubmed] | [DOI]
40 MicroRNA-296 mediated corneal neovascularization in an animal model of corneal burns after alkali exposures
Kai-Bao Ji, Ling Ling, Qian Zhang, Jing-Jing Chou, Xia-Ling Yang, Zhi-Hong Wang, Li Yin, Shu-Fang Wu, Yi-Feng Yu
Experimental and Therapeutic Medicine. 2017;
[Pubmed] | [DOI]
41 Analysis of miRNAs and their target genes associated with lipid metabolism in duck liver
Jun He, Weiqun Wang, Lizhi Lu, Yong Tian, Dong Niu, Jindong Ren, Liyan Dong, Siwei Sun, Yan Zhao, Li Chen, Jianliang Shen, Xiuhong Li
Scientific Reports. 2016; 6(1)
[Pubmed] | [DOI]
42 Prognostic significance of miR-1268a expression and its beneficial effects for post-operative adjuvant transarterial chemoembolization in hepatocellular carcinoma
Yun-Long Lu, Jin-Guang Yao, Xiao-Ying Huang, Chao Wang, Xue-Min Wu, Qiang Xia, Xi-Dai Long
Scientific Reports. 2016; 6(1)
[Pubmed] | [DOI]
43 mirPRo–a novel standalone program for differential expression and variation analysis of miRNAs
Jieming Shi, Min Dong, Lei Li, Lin Liu, Agustin Luz-Madrigal, Panagiotis A. Tsonis, Katia Del Rio-Tsonis, Chun Liang
Scientific Reports. 2015; 5(1)
[Pubmed] | [DOI]


Print this article  Email this article


    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
  Related articles
    Article in PDF (438 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  

    The mirna and si...
   Role in physiology
   Role in pathology
    The Clinical Pot...
   Biogenesis Of MIRNAs

 Article Access Statistics
    PDF Downloaded829    
    Comments [Add]    
    Cited by others 43    

Recommend this journal

© Journal of Oral and Maxillofacial Pathology | Published by Wolters Kluwer - Medknow
Online since 15th Aug, 2007