A Pleiotropically Acting MicroRNA, miR-31, Inhibits Breast Cancer Metastasis (Retracted article. See vol. 161, pg. 417, 2015)

作者：Valastyan Scott; Reinhardt Ferenc; Benaich Nathan; Calogrias Diana; Szasz Attila M; Wang Zhigang C; Brock Jane E; Richardson Andrea L; Weinberg Robert A^*

来源：Cell, 2009, 137(6): 1032-1046.

DOI：10.1016/j.cell.2009.03.047

MicroRNAs are well suited to regulate tumor metastasis because of their capacity to coordinately repress numerous target genes, thereby potentially enabling their intervention at multiple steps of the invasion-metastasis cascade. We identify a microRNA exemplifying these attributes, miR-31, whose expression correlates inversely with metastasis in human breast cancer patients. Overexpression of miR-31 in otherwise-aggressive breast tumor cells suppresses metastasis. We deploy a stable microRNA sponge strategy to inhibit miR-31 in vivo; this allows otherwise-nonaggressive breast cancer cells to metastasize. These phenotypes do not involve confounding influences on primary tumor development and are specifically attributable to miR-31-mediated inhibition of several steps of metastasis, including local invasion, extravasation or initial survival at a distant site, and metastatic colonization. Such pleiotropy is achieved via coordinate repression of a cohort of metastasis-promoting genes, including RhoA. Indeed, RhoA re-expression partially reverses miR-31-imposed metastasis suppression. These findings indicate that miR-31 uses multiple mechanisms to oppose metastasis.

• 出版日期2009-6-12