|Conserved secondary structure of mir-31|
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. From its typical abundance in healthy tissue is a moderate decrease in non-metastatic breast cancer cell lines, and levels are almost completely absent in mouse and human metastatic breast cancer cell lines. There has also been observed a strong encapsulation of tumour cells expressing miR-31, as well as a reduced cell survival rate. miR-31's antimetastatic effects therefore make it a potential therapeutic target for breast cancer.
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.
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. 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.
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. 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. 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.
miR-31 has further been shown to negatively regulate FOXP3, the master regulator in T-lymphocyte development and function. This is through direct binding of miR-31 at its target site in the 3'UTR of FOXP3 mRNA.
- O'Day, E; Lal, A (2010). "MicroRNAs and their target gene networks in breast cancer.". Breast cancer research : BCR 12 (2): 201. doi:10.1186/bcr2484. PMC 2879559. PMID 20346098.
- Valastyan S, Reinhardt F, Benaich N, Calogrias D, Szász AM, Wang ZC et al. (2009). "A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis.". Cell 137 (6): 1032–46. doi:10.1016/j.cell.2009.03.047. PMC 2766609. PMID 19524507.
- Valastyan S, Chang A, Benaich N, Reinhardt F, Weinberg RA (2011). "Activation of miR-31 function in already-established metastases elicits metastatic regression.". Genes Dev 25 (6): 646–59. doi:10.1101/gad.2004211. PMC 3059837. PMID 21406558.
- 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): 136–41. doi:10.1038/embor.2010.208. PMC 3049433. PMID 21212803.
- 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): 136–41. doi:10.1038/embor.2010.208. PMC 3049433. PMID 21212803.
- 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): 31–8. PMID 8381161.
- 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): 1906–15. doi:10.1158/0008-5472.CAN-09-3875. PMC 2831102. PMID 20179198.
- 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): 685–9. doi:10.1007/s12032-009-9269-x. PMID 19598010.
- 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): 1608–18. doi:10.1002/eji.200838509. PMID 19408243.
- 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): 924–30. doi:10.4049/jimmunol.1002218. PMC 3038632. PMID 21149603.
- 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): 221–31. 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): 35293–302. doi:10.1074/jbc.M110.160069. PMC 2975153. PMID 20826792.
- Valastyan S, Chang A, Benaich N, Reinhardt F, Weinberg RA (2010). "Concurrent suppression of integrin alpha5, radixin, and RhoA phenocopies the effects of miR-31 on metastasis.". Cancer Res 70 (12): 5147–54. doi:10.1158/0008-5472.CAN-10-0410. PMC 2891350. PMID 20530680.
- Valastyan S, Weinberg RA (2010). "miR-31: A crucial overseer of tumor metastasis and other emerging roles.". Cell Cycle 9 (11). PMID 20505365.
- Pedrioli DM, Karpanen T, Dabouras V, Jurisic G, van de Hoek G, Shin JW, Marino D, KÃ¤lin RE, Leidel S, Cinelli P, Schulte-Merker S, BrÃ¤ndli AW, Detmar M (2010). "miR-31 functions as a negative regulator of lymphatic vascular lineage-specific differentiation in vitro and vascular development in vivo.". Mol Cell Biol 30 (14): 3620–34. 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): 22809–17. doi:10.1074/jbc.M110.100354. PMC 2906272. PMID 20463022.