Mir-31

Precursor microRNA family

RNA family

mir-31

Conserved secondary structure of mir-31

Identifiers
Symbol| mir-31
Rfam| RF00661
miRBase family| MIPF0000064
Other data
RNA type| microRNA
Domain(s)| Eukaryota
PDB structures| PDBe

miR-31 has been characterised as a tumour suppressor miRNA, with its levels varying in breast cancer cells according to the metastatic state of the tumour.[1] Mir-31-5p has also been observed upregulated in Zinc Deficient rats compared to normal in ESCC (Esophageal Squamous Cell Carcinoma) and in other types of cancers when using this animal model.[2] miR-31's antimetastatic effects therefore make it a potential therapeutic target for breast cancer.

## Functions

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mir-31 has been linked to Duchenne muscular dystrophy − a genetic disorder characterised by a lack of the protein dystrophin − as a potential therapeutic target. Duchenne muscular dystrophy is caused by mutations arising in the dystrophin gene, which impair the translation of dystrophin through the formation of premature termination codons.[3]

miR-31 overexpression is more abundant in human Duchenne muscular dystrophy than in healthy controls, with levels remaining high only in Duchenne muscular dystrophy myoblasts. miR-31 levels in healthy controls are instead decreased with the onset of cell differentiation. miR-31 is part of the circuit controlling late muscle differentiation by repression of dystrophin synthesis, and its expression is localised specifically to regenerating myoblasts of dystrophic muscles.[4] miR-31 is believed to repress the expression of dystrophin by antisense binding of the dystrophin mRNA 3′ untranslated region, and in this way it is thought that miR-31 manipulation could aid treatment for Duchenne muscular dystrophy.

## Applications

[edit]

In serous ovarian cancer, miR-31 is frequently deleted and is the most underexpressed microRNA in this cancer type. It has been shown to affect the levels of gene transcription factor p53, responsible for encoding the tumour suppressor protein p53.[5] Cancer cell lines with an inactive p53 pathway show a vulnerability to miR-31 overexpression, whilst there is resistance to overexpression in cell lines with a functional p53 pathway.[6] miR-31 overexpression is associated with a better prognosis in tumours, suggesting that therapeutic delivery of miR-31 may be beneficial in patients with p53-deficient cancers. Conversely, in gastric cancer miR-31 levels have been found to be significantly lower in tumour cells relative to healthy cells, meaning further potential for use as a diagnostic marker.[7] However, high expression levels of miR-31 correlate to shorter survival in patients with malignant pleural mesothelioma, whereas longer survival has been associated with normal/low expression of miR-31 from blood-based samples.[8] Furthermore, in vivo, anti-miR-31 has proved to reduce miR-31-5p overexpression suppressing the esophageal preneoplasia in Zinc deficient rats. This leads to the repression of miR-31-5p target Stk40 by the inhibition of the STK40-NF-κΒ-controlled inflammatory pathway, with resultant decreased cellular proliferation and activated apoptosis. Notably Zn replenishment is able to restore the regulation of miR-31-5p targets leading to a normal esophageal phenotype.[9] miR-31 has further been shown to negatively regulate FOXP3, the master regulator in T-lymphocyte development and function.[10] This is through direct binding of miR-31 at its target site in the 3′UTR of FOXP3 mRNA.[11]

## References

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1. ^ O'Day, E; Lal, A (2010). "MicroRNAs and their target gene networks in breast cancer". Breast Cancer Research. 12 (2): 201. doi:10.1186/bcr2484. PMC 2879559. PMID 20346098.
2. ^ Fong LY, Taccioli C, Jing R, Smalley KJ, Alder H, Jiang Y, Fadda P, Farber JL, Croce CM (2016). "MicroRNA dysregulation and esophageal cancer development depend on the extent of zinc dietary deficiency". Oncotarget. 7 (10): 10723–38\. doi:10.18632/oncotarget.7561. PMC 4905434. PMID 26918602.
3. ^ Cacchiarelli, D; Incitti, T; Martone, J; Cesana, M; Cazzella, V; Santini, T; Sthandier, O; Bozzoni, I (February 2011). "miR-31 modulates dystrophin expression: new implications for Duchenne muscular dystrophy therapy". EMBO Reports. 12 (2): 136–141\. doi:10.1038/embor.2010.208. PMC 3049433. PMID 21212803.
4. ^ Cacchiarelli D, Incitti T, Martone J, Cesana M, Cazzella V, Santini T, et al. (2011). "miR-31 modulates dystrophin expression: new implications for Duchenne muscular dystrophy therapy". EMBO Rep. 12 (2): 136–141\. doi:10.1038/embor.2010.208. PMC 3049433. PMID 21212803.
5. ^ Louis DN, von Deimling A, Chung RY, Rubio MP, Whaley JM, Eibl RH, et al. (1993). "Comparative study of p53 gene and protein alterations in human astrocytic tumors". J Neuropathol Exp Neurol. 52 (1): 31–38\. doi:10.1097/00005072-199301000-00005. PMID 8381161. S2CID 21836130.
6. ^ Creighton CJ, Fountain MD, Yu Z, Nagaraja AK, Zhu H, Khan M, et al. (2010). "Molecular profiling uncovers a p53-associated role for microRNA-31 in inhibiting the proliferation of serous ovarian carcinomas and other cancers". Cancer Res. 70 (5): 1906–1915\. doi:10.1158/0008-5472.CAN-09-3875. PMC 2831102. PMID 20179198.
7. ^ Zhang, Y; Guo, J; Li, D; Xiao, B; Miao, Y; Jiang, Z; Zhuo, H (September 2010). "Down-regulation of miR-31 expression in gastric cancer tissues and its clinical significance". Medical Oncology (Northwood, London, England). 27 (3): 685–689\. doi:10.1007/s12032-009-9269-x. PMID 19598010. S2CID 22851497.
8. ^ Reid, Glen (June 2015). "MicroRNAs in mesothelioma: from tumour suppressors and biomarkers to therapeutic targets". Journal of Thoracic Disease. 7 (6): 1031–1040\. doi:10.3978/j.issn.2072-1439.2015.04.56. PMC 4466421. PMID 26150916.
9. ^ Cristian Taccioli; Michela Garofalo; Hongping Chen; Yubao Jiang; Guidantonio Malagoli Tagliazucchi; Gianpiero Di Leva; Hansjuerg Alder; Paolo Fadda; Justin Middleton; Karl J Smalley; Tommaso Selmi; Srivatsava Naidu; John L Farber; Carlo M Croce; Louise Y Fong (2015). "Repression of Esophageal Neoplasia and Inflammatory Signaling by Anti-miR-31 Delivery In Vivo". J Natl Cancer Inst. 107 (11): 1–11\. doi:10.1093/jnci/djv220. PMC 4675101. PMID 26286729.
10. ^ Rouas R, Fayyad-Kazan H, El Zein N, Lewalle P, Rothé F, Simion A, et al. (2009). "Human natural Treg microRNA signature: role of microRNA-31 and microRNA-21 in FOXP3 expression". Eur J Immunol. 39 (6): 1608–1618\. doi:10.1002/eji.200838509. PMID 19408243.
11. ^ Divekar AA, Dubey S, Gangalum PR, Singh RR (2011). "Dicer insufficiency and microRNA-155 overexpression in lupus regulatory T cells: an apparent paradox in the setting of an inflammatory milieu". J Immunol. 186 (2): 924–930\. doi:10.4049/jimmunol.1002218. PMC 3038632. PMID 21149603.

## Further reading

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* Olaru AV, Selaru FM, Mori Y, Vazquez C, David S, Paun B, Cheng Y, Jin Z, Yang J, Agarwal R, Abraham JM, Dassopoulos T, Harris M, Bayless TM, Kwon J, Harpaz N, Livak F, Meltzer SJ (2010). "Dynamic changes in the expression of MicroRNA-31 during inflammatory bowel disease-associated neoplastic transformation". Inflamm Bowel Dis. 17 (1): 221–231\. doi:10.1002/ibd.21359. PMC 3006011. PMID 20848542.
* Cottonham CL, Kaneko S, Xu L (2010). "miR-21 and miR-31 converge on TIAM1 to regulate migration and invasion of colon carcinoma cells". J Biol Chem. 285 (46): 35293–35302\. doi:10.1074/jbc.M110.160069. PMC 2975153. PMID 20826792.
* Valastyan S, Weinberg RA (2010). "miR-31: A crucial overseer of tumor metastasis and other emerging roles". Cell Cycle. 9 (11): 2124–2129\. doi:10.4161/cc.9.11.11843. PMID 20505365.
* Pedrioli DM, Karpanen T, Dabouras V, Jurisic G, van de Hoek G, Shin JW, Marino D, Kälin RE, Leidel S, Cinelli P, Schulte-Merker S, Brändli AW, Detmar M (2010). "miR-31 functions as a negative regulator of lymphatic vascular lineage-specific differentiation in vitro and vascular development in vivo" (PDF). Mol Cell Biol. 30 (14): 3620–3634\. doi:10.1128/MCB.00185-10. PMC 2897549. PMID 20479124.
* Ivanov SV, Goparaju CM, Lopez P, Zavadil J, Toren-Haritan G, Rosenwald S, Hoshen M, Chajut A, Cohen D, Pass HI (2010). "Pro-tumorigenic effects of miR-31 loss in mesothelioma". J Biol Chem. 285 (30): 22809–22817\. doi:10.1074/jbc.M110.100354. PMC 2906272. PMID 20463022.

## External links

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*   * Page for mir-31 microRNA precursor family at Rfam

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