miR-138
miR-138 is a family of microRNA precursors found in animals, including humans.[1] MicroRNAs are typically transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~22 nucleotide product.[2] The excised region or, mature product, of the miR-138 precursor is the microRNA mir-138.
miR-138 | |
---|---|
Conserved secondary structure of miR-138 prescursor | |
Identifiers | |
Symbol | miR-138 |
Rfam | RF00671 |
miRBase | MI0000476 |
miRBase family | MIPF0000075 |
NCBI Gene | 406929 |
HGNC | 31524 |
Other data | |
RNA type | miRNA |
Domain(s) | Animalia |
Locus | Chr. 3 p |
PDB structures | PDBe |
miR-138 has been used as an example of the post-transcriptional regulation of miRNA, due to the finding that while the precursor is expressed ubiquitously, the mature product is found only in specific cell types.[3]
Species distribution
The presence of miR-138 has been detected experimentally in humans (Homo sapiens)[1][4][5] and in different animals including house mouse (Mus musculus),[1][3][4][6][7][8][9] brown rat (Rattus norvegicus),[1][7][10][11][12] platypus (Ornithorhynchus anatinus),[13] Carolina anole(Anolis carolinensis),[14] cattle (Bos taurus),[15][16] common carp (Cyprinus carpio),[17] dog (Canis familiaris),[18] Chinese hamster (Cricetulus griseus),[19] zebrafish (Danio rerio),[20] red junglefowl (Gallus gallus),[21] western gorilla (Gorilla gorilla),[22] gray short-tailed opossum (Monodelphis domestica),[23] Oryzias latipes,[24] sea lamprey (Petromyzon marinus),[25] Tasmanian devil (Sarcophilus harrisii),[26] wild boar (Sus scrofa)[27] and zebra finch (Taeniopygia guttata).[28]
It is also predicted computationally that the miR-138 gene exists in the genome of other animals including horse (Equus caballus),[29] rhesus macaque (Macaca mulatta),[30] takifugu rubripes (Fugu rubripes), Bornean orangutan (Pongo pygmaeus),[31] common chimpanzee (Pan troglodytes),[32] Tetraodon nigroviridis and western clawed frog (Xenopus tropicalis).
Genomic location
In human genome, there are two miR-138 associated genes and they are not located in any cluster. More precisely, the miR-138-1 gene is in region 5 at 3p21.3[33] and miR-138-2 is located on chromosome 16 (16q13).[34]
Pattern of expression
In adult mice, miR-138 is only expressed in brain tissue. Its expression is not uniform throughout the brain but restricted to distinct neuronal populations. On the contrary, its precursor, pre-miR-138-2, is ubiquitously expressed throughout all tissues, which suggests that the expression of miRNAs can be regulated at the post-transcription level.[3]
In the zebrafish, miR-138 is expressed in specific domains in the heart and is required to establish appropriate chamber-specific gene expression patterns.[35]
Targets and function
Since the identification of miR-138, a number of targets have been found and some of them have been verified experimentally. It has been proven that miR-138 is involved in different pathways. Furthermore, it is in relation with various types of cancer.
- HIF-1a
- Hypoxia-inducible factor-1alpha (HIF-1a), one of the key regulators in cancer cells, has been shown to be one target of miR-138.[36]
- VIM, ZEB2, EZH2 and head and neck cancers
- Downregulation of miR-138 has been reported in several types of cancers, including HNSCC(head and neck squamous cell carcinoma). It is suggested that miR-138 is a multi-functional molecular regulator and plays major roles in EMT (epithelial-mesenchymal transition) and in HNSCC progression. A number of miR-138 target genes have been identified to be associated with EMT, including VIM (vimentin), ZEB2 (zinc finger E-box-binding homeobox 2) and EZH2 (enhancer of zeste homologue 2).[37]
- CCND1 and nasopharyngeal carcinoma
- miR-138 is commonly underexpressed in nasopharyngeal carcinoma (NPC) specimens and NPC cell lines. Cyclin D1 (CCND1), which is widely upregulated in NPC tumors, is found as a direct target of miR-138. Therefore, miR-138 might be a tumor suppressor in NPC, which is exerted partially by inhibiting CCND1 expression.[38]
- BCR-ABL and CCND3
- BCR (breakpoint cluster region)-ABL (c-abl oncogene 1, non-receptor tyrosine kinase)/GATA1/miR-138 mini circuitry contributes to the leukemogenesis of chronic myeloid leukemia (CML). ABL and BCR-ABL are the target genes of miR-138, which binds to the coding region instead of three prime untranslated region (3'UTR). miR-138 can negatively regulate another gene CCND3 via binding to its 3'-UTR. The expression of miR-138 is activated by GATA1, which in turn is repressed by BCR-ABL. Therefore, miR-138, by virtue of a BCR-ABL/GATA1/miR-138 circuitry, is a tumor suppressor miRNA implicated in the pathogenesis of CML and its clinical response to imatinib.[39]
- H2AX and DNA damage repair
- mir-138 is linked with DNA damage repair. It can directly target the histone H2AX 3'UTR, reduce histone H2AX expression and induce chromosomal instability after DNA damage.[40]
- ALDH1A2 and CSPG2
- In zebrafish, the mature form of miR-138 regulates gene expression influencing cardiac development. miR-138 helps establish discrete domains of gene expression during cardiac morphogenesis by targeting multiple members of a common pathway. It has been experimentally verified that miR-138 can negatively regulate aldh1a2, encoding retinoic acid (RA) dehydrogenase (Raldh2), by targeting the binding site in the 3'UTR of its mRNA. Another putative target of miR-138 is cspg2.[35]
- Regulation of sleep
- In rats, miR-138, let-7b, and miR-125a are expressed at different times and in different structures in the brain and likely play a role in the regulation of sleep.[41]
- Brain cancer
- miR-138 has been found to be significantly linked with the formation and growth of Gliomas, from Cancerous Stem Cells (CSC). In vitro inhibition of miR-138 prevents tumour sphere formation. Furthermore, its high expression in Glioma makes it a potential biomarker for CSC.[42]
- Rhoc, ROCK2 and Tongue cancer
- Tumour metastasis concerning the Tongue Squamous Cell Carcinoma (TSCC) can be regulated via the expression of 2 key genes in Rho GTPase signaling pathway : RhoC and ROCK2 (Rho-associated protein kinase 2). Thus, by targeting the 3' untranslated region of those genes, mir-138 is able to reduce their expression and by this mean, to destroy TSCC ability migrate and invade.[43]
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Further reading
- Pignot G, Cizeron-Clairac G, Vacher S, Susini A, Tozlu S, Vieillefond A, Zerbib M, Lidereau R, Debre B, Amsellem-Ouazana D, Bieche I (Jun 2013). "microRNA expression profile in a large series of bladder tumors: identification of a 3-miRNA signature associated with aggressiveness of muscle-invasive bladder cancer". International Journal of Cancer. 132 (11): 2479–91. doi:10.1002/ijc.27949. PMID 23169479. S2CID 44558161.
- Ye D, Wang G, Liu Y, Huang W, Wu M, Zhu S, Jia W, Deng AM, Liu H, Kang J (Aug 2012). "MiR-138 promotes induced pluripotent stem cell generation through the regulation of the p53 signaling". Stem Cells. 30 (8): 1645–54. doi:10.1002/stem.1149. PMID 22696098. S2CID 10924423.
- Jin Y, Wang C, Liu X, Mu W, Chen Z, Yu D, Wang A, Dai Y, Zhou X (Nov 2011). "Molecular characterization of the microRNA-138-Fos-like antigen 1 (FOSL1) regulatory module in squamous cell carcinoma". The Journal of Biological Chemistry. 286 (46): 40104–9. doi:10.1074/jbc.c111.296707. PMC 3220531. PMID 21969367.
- Eskildsen T, Taipaleenmäki H, Stenvang J, Abdallah BM, Ditzel N, Nossent AY, Bak M, Kauppinen S, Kassem M (Apr 2011). "MicroRNA-138 regulates osteogenic differentiation of human stromal (mesenchymal) stem cells in vivo". Proceedings of the National Academy of Sciences of the United States of America. 108 (15): 6139–44. doi:10.1073/pnas.1016758108. PMC 3076836. PMID 21444814.
- Muiños-Gimeno M, Espinosa-Parrilla Y, Guidi M, Kagerbauer B, Sipilä T, Maron E, Pettai K, Kananen L, Navinés R, Martín-Santos R, Gratacòs M, Metspalu A, Hovatta I, Estivill X (Mar 2011). "Human microRNAs miR-22, miR-138-2, miR-148a, and miR-488 are associated with panic disorder and regulate several anxiety candidate genes and related pathways". Biological Psychiatry. 69 (6): 526–33. doi:10.1016/j.biopsych.2010.10.010. PMID 21168126. S2CID 206101163.
- Kisliouk T, Yosefi S, Meiri N (Jan 2011). "MiR-138 inhibits EZH2 methyltransferase expression and methylation of histone H3 at lysine 27, and affects thermotolerance acquisition". The European Journal of Neuroscience. 33 (2): 224–35. doi:10.1111/j.1460-9568.2010.07493.x. PMID 21070394. S2CID 205516595.
- Yang Z, Bian C, Zhou H, Huang S, Wang S, Liao L, Zhao RC (Feb 2011). "MicroRNA hsa-miR-138 inhibits adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells through adenovirus EID-1". Stem Cells and Development. 20 (2): 259–67. doi:10.1089/scd.2010.0072. PMID 20486779.
External links
Category:MicroRNA