Biology:mir-184

From HandWiki
Short description: Non-coding microRNA molecule
mir-184
MiR-184 secondary structure.png
miR-184 microRNA secondary structure and sequence conservation
Identifiers
Symbolmir-184
RfamRF00657
miRBase familyMIPF0000059
NCBI Gene406960
HGNC31555
OMIM613146
Other data
RNA typemicroRNA
Domain(s)Eukaryota; Chordata
PDB structuresPDBe

In molecular biology, miR-184 microRNA is a short non-coding RNA molecule. MicroRNAs (miRNAs) function as posttranscriptional regulators of expression levels of other genes by several mechanisms.[1] Several targets for miR-184 have been described, including that of mediators of neurological development, apoptosis and it has been suggested that miR-184 plays an essential role in development.[2]

MicroRNAs can bind to the three prime untranslated region (3'UTR) of the target messenger RNA (mRNA).[3] Binding of the miRNA can hinder translation of mRNA by promoting degradation or inducing deadenylation.[4]

Genomic location

miR-184 is a single copy gene and evolutionarily conserved at the nucleotide level from flies to humans.[5] In humans, miR-184 is located within region 25.1 on the q-arm of chromosome 15, and its corresponding transcript is comparatively small (84bp) which is not encoded near other clustered miRNAs.[6] In the mouse genome, miR-184 is located in an imprinted locus on mouse chromosome 9, and it is 55 kb away from the nearest coding gene.[7]

The genomic region immediately surrounding miR-184 does not contain a classic CpG island, but does contain several CpG-rich sequences that are suitable for MBD1 binding.[8]

Expression

miR-184 displays a tissue- and developmental-specific expression pattern. In mammals, mature miR-184 is particularly enriched in the brain and testis,[7] along with the corneal epithelium.[9] Depolarization of cortical neurons results in pri-miR-184 expression in an allele specific manner.[7] High expression is observed in suprabasal cells of the corneal epithelium in the mouse model, along with expression in mouse testis and brain tissue.[7][9] In Zebrafish, it is expressed in lens, hatching gland and epidermis (shown by Northern blot).[10] miR-184 is expressed ubiquitously in Drosophila embryos, larvae and adults, and its expression pattern displays dynamic changes during the development of embryo, especially in the central nervous system.[2][5] However, the temporal and spatial expression pattern of miR-184 is still being debated.

Role in neuronal cells

C. Liu et al. showed that Methyl-CpG binding protein 1 (MBD1) regulates the expression of several miRNAs in adult neural stem/progenitor cells (aNSCs) and, specifically, that miR-184 is directly repressed by MBD1. High levels of miR-184 promotes cell proliferation but inhibits differentiation of aNSCs, whereas inhibition of miR-184 rescued phenotypes associated with MBD1 deficiency.[11]

Numblike (Numbl) is known to be important in embryonic neural stem cell function and cortical brain development and has been identified as a downstream target of miR-184.[12][13] It has been found that exogenously expressed Numbl could rescue aNSC proliferation and differentiation deficits resulting from either elevated miR-184 or MBD1 deficiency.[11]

Other Targets

An analysis of the primary transcript of miR-184 (pri-mir-184) in several mouse tissues revealed specific expression in the brain and testis. Its expression is repressed by the binding of methyl-CpG binding protein 2 (MeCP2) to its promoter, but is upregulated by the release of MeCP2 after depolarization, suggesting a link between miRNAs and DNA methylation pathways .[7] J. Yu et al. demonstrated that the lipid phosphatase SH2-containing phosphoinositide 5'phosphatase 2 (SHIP2) is a target of miRNA-205 (miR-205) in epithelial cells, and that the corneal epithelial-specific miR-184 can interfere with the ability of miR-205 to suppress SHIP2 levels. The mechanism by which miR-184 negatively regulates miR-205 appears to be unique, and is the first example of a miRNA negatively regulating another to maintain levels of a target protein. miR-184 does not directly affect SHIP2 translation, but instead prevents miR-205 from interacting with SHIP2 mRNA. Interfering with miR-205 function by using a synthetic antagomir, or by the ectopic expression of miR-184, is thought to lead to a coordinated damping of the Akt signaling pathway via SHIP2 induction.[14]

R. Weitzel et al. showed that miR-184 mediates NFAT1 translational regulation in umbilical cord blood (UCB) graft CD4+ T-cells leading to blunted allogenic responses.[15]

J. Roberts et al. found that miR-184 repressed the expression of Argonaute 2 in epidermal keratinocytes.[16] Similarly, Tattikota et al. showed miR-184 reduced Argonaute 2 levels in the MIN6 mouse pancreatic beta islet cell line.[17]

Furthermore, miR-184 has multiple roles in Drosophila female germline development.[18]

Finally, a recent study identified miR-184 as essential for embryonic corneal commitment of pluripotent stem cells.[19]

Disease relevance

• A single base mutation in the seed region of miR-184 causes EDICT syndrome, a hereditary eye disease.[20]
• A mutation altering the miR-184 seed region causes familial keratoconus with cataract.[21]
• Rett syndrome.[7]
• Several forms of cancer (see below) including elevation of miR-184 levels in squamous cell carcinoma of the tongue.[22] All-trans-retinoic acid induces miR-184 expression in neuroblastoma cell line and ectopic miR-184 causes apoptosis.[23]
• miR-184 has been implicated in ischemia-induced retinal neovascularization.[24]

Angiogenesis and cancer

Dysregulation of miRNA expression is thought to play a part in abnormal gene expression in cancer cells, and miR-184 has been implicated in several forms of cancer.[22][25] MYCN has been found to contribute to tumorigenesis, in part, by repressing miR-184, leading to increased levels of the serine/threonine kinase, AKT2. AKT2 is a major effector of the phosphatidylinositol 3-kinase (PI3K) pathways, one of the most potent survival pathways in cancer, and is a direct target of miR-184. It has been suggested that MYCN provides a tumourigenic effect, in part, by protecting AKT2 mRNA from degradation by miR-184, permitting the PI3K pathway to remain functional.[26]

miR-184 has been found to be significantly increased in the tumor cells in comparison with the normal epithelial cells of the tongue. High miR-184 levels were not only detected in the tumor tissues, but also in the plasma of patients with tongue squamous cell carcinoma (SCC). Decreased plasma levels of miR-184 were observed in patients after surgical removal of the primary tumor, suggesting that it is a potential oncogenic miRNA in tongue SCC. Inhibiting miR-184 promotes apoptosis as well as hindering cell proliferation in cultured tongue SCC cells.[27] Furthermore, over expression of miR-184 in neuroblastoma cell lines results in apoptosis.[23] SND1 expression is regulated by miR-184 in gliomas.[28]

See also

References

  1. ↑ Cullen BR (December 2004). "Transcription and processing of human microRNA precursors". Mol. Cell 16 (6): 861–5. doi:10.1016/j.molcel.2004.12.002. PMID 15610730. 
  2. ↑ 2.0 2.1 "Localized expression pattern of miR-184 in Drosophila". Mol Biol Rep 38 (1): 355–8. March 2010. doi:10.1007/s11033-010-0115-1. PMID 20339929. 
  3. ↑ "RNAi: nature abhors a double-strand". Curr. Opin. Genet. Dev. 12 (2): 225–32. April 2002. doi:10.1016/S0959-437X(02)00290-3. PMID 11893497. 
  4. ↑ "A microRNA in a multiple-turnover RNAi enzyme complex". Science 297 (5589): 2056–60. September 2002. doi:10.1126/science.1073827. PMID 12154197. Bibcode: 2002Sci...297.2056H. 
  5. ↑ 5.0 5.1 "Drosophila microRNAs exhibit diverse spatial expression patterns during embryonic development". Proc. Natl. Acad. Sci. U.S.A. 102 (50): 18017–22. December 2005. doi:10.1073/pnas.0508823102. PMID 16330759. Bibcode: 2005PNAS..10218017A. 
  6. ↑ "Reduced methyl-CpG protein binding contributing to miR-184 expression in umbilical cord blood CD4(+) T-cells". Leukemia 25 (1): 169–72. October 2010. doi:10.1038/leu.2010.227. PMID 20927133. 
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 "MeCP2-dependent repression of an imprinted miR-184 released by depolarization". Hum. Mol. Genet. 17 (8): 1192–9. April 2008. doi:10.1093/hmg/ddn011. PMID 18203756. 
  8. ↑ "Mbd1 is recruited to both methylated and nonmethylated CpGs via distinct DNA binding domains". Mol. Cell. Biol. 24 (8): 3387–95. April 2004. doi:10.1128/mcb.24.8.3387-3395.2004. PMID 15060159. 
  9. ↑ 9.0 9.1 "MicroRNAs of the mammalian eye display distinct and overlapping tissue specificity". Mol. Vis. 12: 1175–84. 2006. PMID 17102797. 
  10. ↑ "MicroRNA expression in zebrafish embryonic development". Science 309 (5732): 310–1. July 2005. doi:10.1126/science.1114519. PMID 15919954. Bibcode: 2005Sci...309..310W. 
  11. ↑ 11.0 11.1 "Epigenetic regulation of miR-184 by MBD1 governs neural stem cell proliferation and differentiation". Cell Stem Cell 6 (5): 433–44. May 2010. doi:10.1016/j.stem.2010.02.017. PMID 20452318. 
  12. ↑ "Inactivation of Numb and Numblike in embryonic dorsal forebrain impairs neurogenesis and disrupts cortical morphogenesis". Neuron 40 (6): 1105–18. December 2003. doi:10.1016/S0896-6273(03)00755-4. PMID 14687546. 
  13. ↑ "Progenitor cell maintenance requires numb and numblike during mouse neurogenesis". Nature 419 (6910): 929–34. October 2002. doi:10.1038/nature01124. PMID 12410312. Bibcode: 2002Natur.419..929P. 
  14. ↑ "MicroRNA-184 antagonizes microRNA-205 to maintain SHIP2 levels in epithelia". Proc. Natl. Acad. Sci. U.S.A. 105 (49): 19300–5. December 2008. doi:10.1073/pnas.0803992105. PMID 19033458. Bibcode: 2008PNAS..10519300Y. 
  15. ↑ "microRNA 184 regulates expression of NFAT1 in umbilical cord blood CD4+ T cells". Blood 113 (26): 6648–57. June 2009. doi:10.1182/blood-2008-09-181156. PMID 19286996. 
  16. ↑ "Expression of microRNA-184 in keratinocytes represses argonaute 2". J. Cell. Physiol. 228 (12): 2314–23. 2013. doi:10.1002/jcp.24401. PMID 23696368. 
  17. ↑ "Argonaute2 mediates compensatory expansion of the pancreatic β cell". Cell Metab. 19 (1): 122–34. 2014. doi:10.1016/j.cmet.2013.11.015. PMID 24361012. 
  18. ↑ "miR-184 has multiple roles in Drosophila female germline development". Dev. Cell 17 (1): 123–33. July 2009. doi:10.1016/j.devcel.2009.06.008. PMID 19619497. 
  19. ↑ "Pluripotent stem cell model reveals essential roles for miR-450b-5p and miR-184 in embryonic corneal lineage specification". Stem Cells 30 (5): 898–909. May 2012. doi:10.1002/stem.1068. PMID 22367714. 
  20. ↑ "A Single-Base Substitution in the Seed Region of miR-184 Causes EDICT Syndrome", Invest. Ophthalmol. Vis. Sci. 53 (1): 348–53, January 2012, doi:10.1167/iovs.11-8783, PMID 22131394, PMC 3292370, http://www.iovs.org/content/53/1/348 
  21. ↑ "Mutation Altering the miR-184 Seed Region Causes Familial Keratoconus with Cataract". American Journal of Human Genetics 89 (5): 628–33. 2011. doi:10.1016/j.ajhg.2011.09.014. PMID 21996275. 
  22. ↑ 22.0 22.1 "Mature miR-184 as Potential Oncogenic microRNA of Squamous Cell Carcinoma of Tongue". Clin. Cancer Res. 14 (9): 2588–92. May 2008. doi:10.1158/1078-0432.CCR-07-0666. PMID 18451220. 
  23. ↑ 23.0 23.1 "Differential patterns of microRNA expression in neuroblastoma are correlated with prognosis, differentiation, and apoptosis". Cancer Res. 67 (3): 976–83. February 2007. doi:10.1158/0008-5472.CAN-06-3667. PMID 17283129. 
  24. ↑ "MicroRNAs regulate ocular neovascularization". Mol. Ther. 16 (7): 1208–16. July 2008. doi:10.1038/mt.2008.104. PMID 18500251. 
  25. ↑ "A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation". Cancer Res. 65 (21): 9628–32. November 2005. doi:10.1158/0008-5472.CAN-05-2352. PMID 16266980. 
  26. ↑ "MicroRNA-184 inhibits neuroblastoma cell survival through targeting the serine/threonine kinase AKT2". Mol. Cancer 9: 83. 2010. doi:10.1186/1476-4598-9-83. PMID 20409325. 
  27. ↑ "Mature miR-184 and squamous cell carcinoma of the tongue". ScientificWorldJournal 9: 130–2. 2009. doi:10.1100/tsw.2009.12. PMID 19219377. 
  28. ↑ "Suppression of miR-184 in malignant gliomas upregulates SND1 and promotes tumor aggressiveness". Neuro-Oncology 17 (3): 419–29. 2015. doi:10.1093/neuonc/nou220. PMID 25216670. 

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