microRNA of the Month: microRNA-31

MicroRNA-31 earns the honor of microRNA of the month due to its varied function in the areas of cell development, cancer, and immunology.

Cell Development
By targeting a number of growth regulatory molecules and cytoskeletal proteins, miR-31 is involved in establishing an optimal balance of gene expression in the hair follicle required for its proper growth and hair fiber formation.¹

Cancer
miR-31 is prominently overexpressed in mouse lung cancers and knockdown of miR-31 substantially represses lung cancer cell growth.  Several tumor-suppressive genes, such as large tumor suppressor 2 (LATS2) and PP2A regulatory subunit B alpha isoform (PPP2R2A), have been identified as miR-31 targets.  These target mRNAs and miR-31 are inversely expressed in mouse and human lung cancers.²

miR-31 is the most underexpressed microRNA in serous ovarian cancer and functional overexpression of miR-31 inhibits the proliferation of serous ovarian carcinomas in cell lines with dysfunctional p53 pathways while not affecting cell lines with functional p53). Predicted miR-31 targets include genes that promotes p53 activity and miR-31 overexpression induced a global gene expression pattern associated with better prognosis in tumors, suggesting that patients with cancers deficient in p53 activity might benefit from therapeutic delivery of miR-31.³

Immunology
FOXP3 is the master regulator in the development and function of regulatory T cells.  miR-31, normally under-expressed in T regulatory cells, negatively regulates FOXP3 expression by binding directly to its target site in the 3′ UTR of FOXP3 mRNA.⁴

1. Mardaryev AN, Ahmed MI, Vlahov NV, Fessing MY, Gill JH, Sharov AA, Botchkareva NV. (2010) Micro-RNA-31 controls hair cycle-associated changes in gene expression programs of the skin and hair follicle. FASEB J [Epub ahead of print]. [abstract]
2. Liu X, Sempere LF, Ouyang H, Memoli VA, Andrew AS, Luo Y, Demidenko E, Korc M, Shi W, Preis M, Dragnev KH, Li H, Direnzo J, Bak M, Freemantle SJ, Kauppinen S, Dmitrovsky E. (2010) MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors. J Clin Invest 120(4), 1298-309. [abstract]
3. Creighton CJ, Fountain MD, Yu Z, Nagaraja AK, Zhu H, Khan M, Olokpa E, Zariff A, Gunaratne PH, Matzuk MM, Anderson ML. (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. [abstract]
4. Rouas R, Fayyad-Kazan H, El Zein N, Lewalle P, Rothé F, Simion A, Akl H, Mourtada M, El Rifai M, Burny A, Romero P, Martiat P, Badran B. (2009) Human natural Treg microRNA signature: role of microRNA-31 and microRNA-21 in FOXP3 expression. Eur J Immunol 39(6), 1608-18. [abstract]