mir-184

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mir-184
Chordata
PDB structuresPDBe

In molecular biology, miR-184 microRNA is a short

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

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

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.

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. PMID 15610730
    .
  2. ^
    S2CID 2939105
    .
  3. PMID 11893497
    .
  4. S2CID 16969059
    .
  5. ^
    PMID 16330759
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  6. PMID 20927133
    .
  7. ^
    PMID 18203756
    .
  8. PMID 15060159
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  9. ^
    PMID 17102797
    .
  10. S2CID 38939571
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  11. ^
    PMID 20452318
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  12. PMID 14687546
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  13. S2CID 4412567
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  14. PMID 19033458
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  15. PMID 19286996
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  16. S2CID 206052733
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  17. PMID 24361012
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  18. PMID 19619497
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  19. PMID 22367714
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  20. PMID 22131394
  21. PMID 21996275
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  22. ^
    PMID 18451220
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  23. ^
    PMID 17283129
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  24. PMID 18500251
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  25. PMID 16266980
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  26. PMID 20409325
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  27. PMID 19219377
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  28. PMID 25216670
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External links
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