Biology:miR-138

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miR-138
Mir-138 SS.png
Conserved secondary structure of miR-138 prescursor
Identifiers
SymbolmiR-138
RfamRF00671
miRBaseMI0000476
miRBase familyMIPF0000075
NCBI Gene406929
HGNC31524
Other data
RNA typemiRNA
Domain(s)Animalia
LocusChr. 3 p
PDB structuresPDBe

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 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] 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]

References

  1. ↑ 1.0 1.1 1.2 1.3 "A mammalian microRNA expression atlas based on small RNA library sequencing". Cell 129 (7): 1401–14. Jun 2007. doi:10.1016/j.cell.2007.04.040. PMID 17604727. 
  2. ↑ "microRNAs: tiny regulators with great potential". Cell 107 (7): 823–6. Dec 2001. doi:10.1016/S0092-8674(01)00616-X. PMID 11779458. 
  3. ↑ 3.0 3.1 3.2 "Post-transcriptional regulation of microRNA expression". RNA 12 (7): 1161–7. Jul 2006. doi:10.1261/rna.2322506. PMID 16738409. 
  4. ↑ 4.0 4.1 "Identification of tissue-specific microRNAs from mouse". Current Biology 12 (9): 735–9. Apr 2002. doi:10.1016/s0960-9822(02)00809-6. PMID 12007417. 
  5. ↑ "Patterns of known and novel small RNAs in human cervical cancer". Cancer Research 67 (13): 6031–43. Jul 2007. doi:10.1158/0008-5472.can-06-0561. PMID 17616659. 
  6. ↑ "New human and mouse microRNA genes found by homology search". The FEBS Journal 272 (1): 59–73. Jan 2005. doi:10.1111/j.1432-1033.2004.04389.x. PMID 15634332. 
  7. ↑ 7.0 7.1 "Identification of many microRNAs that copurify with polyribosomes in mammalian neurons". Proceedings of the National Academy of Sciences of the United States of America 101 (1): 360–5. Jan 2004. doi:10.1073/pnas.2333854100. PMID 14691248. Bibcode: 2004PNAS..101..360K. 
  8. ↑ "MicroRNA transcriptome in the newborn mouse ovaries determined by massive parallel sequencing". Molecular Human Reproduction 16 (7): 463–71. Jul 2010. doi:10.1093/molehr/gaq017. PMID 20215419. 
  9. ↑ "Mammalian microRNAs: experimental evaluation of novel and previously annotated genes". Genes & Development 24 (10): 992–1009. May 2010. doi:10.1101/gad.1884710. PMID 20413612. 
  10. ↑ "Microarray analysis of microRNA expression in the developing mammalian brain". Genome Biology 5 (9): R68. 2004. doi:10.1186/gb-2004-5-9-r68. PMID 15345052. 
  11. ↑ "Cloning and identification of novel microRNAs from rat hippocampus". Acta Biochimica et Biophysica Sinica 39 (9): 708–14. Sep 2007. doi:10.1111/j.1745-7270.2007.00324.x. PMID 17805466. 
  12. ↑ "Small RNA expression and strain specificity in the rat". BMC Genomics 11 (1): 249. 19 April 2010. doi:10.1186/1471-2164-11-249. PMID 20403161. 
  13. ↑ "Conservation of small RNA pathways in platypus". Genome Research 18 (6): 995–1004. Jun 2008. doi:10.1101/gr.073056.107. PMID 18463306. 
  14. ↑ "MicroRNAs support a turtle + lizard clade". Biology Letters 8 (1): 104–7. Feb 2012. doi:10.1098/rsbl.2011.0477. PMID 21775315. 
  15. ↑ "Discovery and profiling of bovine microRNAs from immune-related and embryonic tissues". Physiological Genomics 29 (1): 35–43. Mar 2007. doi:10.1152/physiolgenomics.00081.2006. PMID 17105755. 
  16. ↑ "Identification and expression profiling of microRNAs during bovine oocyte maturation using heterologous approach". Molecular Reproduction and Development 76 (7): 665–77. Jul 2009. doi:10.1002/mrd.21005. PMID 19170227. 
  17. ↑ "Identification and profiling of microRNAs from skeletal muscle of the common carp". PLOS ONE 7 (1): e30925. 2012. doi:10.1371/journal.pone.0030925. PMID 22303472. Bibcode: 2012PLoSO...730925Y. 
  18. ↑ "Discovering microRNAs from deep sequencing data using miRDeep". Nature Biotechnology 26 (4): 407–15. Apr 2008. doi:10.1038/nbt1394. PMID 18392026. 
  19. ↑ "Next-generation sequencing of the Chinese hamster ovary microRNA transcriptome: Identification, annotation and profiling of microRNAs as targets for cellular engineering". Journal of Biotechnology 153 (1–2): 62–75. Apr 2011. doi:10.1016/j.jbiotec.2011.02.011. PMID 21392545. 
  20. ↑ "The developmental miRNA profiles of zebrafish as determined by small RNA cloning". Genes & Development 19 (11): 1288–93. Jun 2005. doi:10.1101/gad.1310605. PMID 15937218. 
  21. ↑ International Chicken Genome Sequencing Consortium (Dec 2004). "Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution". Nature 432 (7018): 695–716. doi:10.1038/nature03154. PMID 15592404. Bibcode: 2004Natur.432..695C. https://escholarship.org/content/qt44v0c3r5/qt44v0c3r5.pdf?t=or4mqz. 
  22. ↑ "Annotation of primate miRNAs by high throughput sequencing of small RNA libraries". BMC Genomics 13 (1): 116. 27 March 2012. doi:10.1186/1471-2164-13-116. PMID 22453055. 
  23. ↑ "In vitro and in silico annotation of conserved and nonconserved microRNAs in the genome of the marsupial Monodelphis domestica". The Journal of Heredity 99 (1): 66–72. January–February 2008. doi:10.1093/jhered/esm085. PMID 17965199. 
  24. ↑ "Discovery and characterization of medaka miRNA genes by next generation sequencing platform". BMC Genomics 11 (Suppl 4): S8. 2 December 2010. doi:10.1186/1471-2164-11-s4-s8. PMID 21143817. 
  25. ↑ "microRNAs reveal the interrelationships of hagfish, lampreys, and gnathostomes and the nature of the ancestral vertebrate". Proceedings of the National Academy of Sciences of the United States of America 107 (45): 19379–83. Nov 2010. doi:10.1073/pnas.1010350107. PMID 20959416. 
  26. ↑ "The Tasmanian devil transcriptome reveals Schwann cell origins of a clonally transmissible cancer". Science 327 (5961): 84–7. Jan 2010. doi:10.1126/science.1180616. PMID 20044575. Bibcode: 2010Sci...327...84M. 
  27. ↑ "MicroRNA identity and abundance in developing swine adipose tissue as determined by Solexa sequencing". Journal of Cellular Biochemistry 112 (5): 1318–28. May 2011. doi:10.1002/jcb.23045. PMID 21312241. 
  28. ↑ "The genome of a songbird". Nature 464 (7289): 757–62. Apr 2010. doi:10.1038/nature08819. PMID 20360741. Bibcode: 2010Natur.464..757W. 
  29. ↑ "In silico detection and characteristics of novel microRNA genes in the Equus caballus genome using an integrated ab initio and comparative genomic approach". Genomics 94 (2): 125–31. Aug 2009. doi:10.1016/j.ygeno.2009.04.006. PMID 19406225. 
  30. ↑ "Identification of novel homologous microRNA genes in the rhesus macaque genome". BMC Genomics 9 (1): 8. 10 January 2008. doi:10.1186/1471-2164-9-8. PMID 18186931. 
  31. ↑ "Genome-wide comparative analysis of microRNAs in three non-human primates". BMC Research Notes 3 (1): 64. 9 March 2010. doi:10.1186/1756-0500-3-64. PMID 20214803. 
  32. ↑ "Computational identification of novel microRNA homologs in the chimpanzee genome". Computational Biology and Chemistry 33 (1): 62–70. Feb 2009. doi:10.1016/j.compbiolchem.2008.07.024. PMID 18760970. 
  33. ↑ "Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers". Proceedings of the National Academy of Sciences of the United States of America 101 (9): 2999–3004. Mar 2004. doi:10.1073/pnas.0307323101. PMID 14973191. Bibcode: 2004PNAS..101.2999C. 
  34. ↑ "MicroRNA-138 suppresses invasion and promotes apoptosis in head and neck squamous cell carcinoma cell lines". Cancer Letters 286 (2): 217–22. Dec 2009. doi:10.1016/j.canlet.2009.05.030. PMID 19540661. 
  35. ↑ 35.0 35.1 "microRNA-138 modulates cardiac patterning during embryonic development". Proceedings of the National Academy of Sciences of the United States of America 105 (46): 17830–5. Nov 2008. doi:10.1073/pnas.0804673105. PMID 19004786. Bibcode: 2008PNAS..10517830M. 
  36. ↑ "MiR-138 suppresses expression of hypoxia-inducible factor 1α (HIF-1α) in clear cell renal cell carcinoma 786-O cells". Asian Pacific Journal of Cancer Prevention 12 (5): 1307–11. 2011. PMID 21875287. 
  37. ↑ "MicroRNA-138 suppresses epithelial-mesenchymal transition in squamous cell carcinoma cell lines". The Biochemical Journal 440 (1): 23–31. Nov 2011. doi:10.1042/BJ20111006. PMID 21770894. 
  38. ↑ "MiR-138 suppressed nasopharyngeal carcinoma growth and tumorigenesis by targeting the CCND1 oncogene". Cell Cycle 11 (13): 2495–506. Jul 2012. doi:10.4161/cc.20898. PMID 22739938. 
  39. ↑ "BCR-ABL/GATA1/miR-138 mini circuitry contributes to the leukemogenesis of chronic myeloid leukemia". Oncogene 33 (1): 44–54. Jan 2014. doi:10.1038/onc.2012.557. PMID 23208504. 
  40. ↑ "MicroRNA-138 modulates DNA damage response by repressing histone H2AX expression". Molecular Cancer Research 9 (8): 1100–11. Aug 2011. doi:10.1158/1541-7786.MCR-11-0007. PMID 21693595. 
  41. ↑ "MicroRNA 138, let-7b, and 125a inhibitors differentially alter sleep and EEG delta-wave activity in rats". Journal of Applied Physiology 113 (11): 1756–62. Dec 2012. doi:10.1152/japplphysiol.00940.2012. PMID 23104698. 
  42. ↑ "Targeting glioma stem cells by functional inhibition of a prosurvival oncomiR-138 in malignant gliomas". Cell Reports 2 (3): 591–602. Sep 2012. doi:10.1016/j.celrep.2012.07.012. PMID 22921398. 
  43. ↑ "Downregulation of the Rho GTPase signaling pathway is involved in the microRNA-138-mediated inhibition of cell migration and invasion in tongue squamous cell carcinoma". International Journal of Cancer 127 (3): 505–12. Aug 2010. doi:10.1002/ijc.25320. PMID 20232393. 

Further reading

External links



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