MICRORNA-196A TARGETS ANNEXIN A1 AND BRAM1 TO REGULATE CELL PROLIFERATION AND MIGRATION IN BREAST AND RENAL CANCER CELLS

Abstract

In this study, microRNA miR-196a was found to promote cell proliferation, migration and drug-sensitivity in both breast and renal cancer cells in vitro. Xenograft of MDA-MB-231 cells overexpressing miR-196a into athymic nude mice confirmed that miR-196a could promote breast tumor growth. We demonstrate that miR-196a directly targets the 3?-untranslated region (3?UTR) of Annexin-1 (ANXA1) and the rescue assay indicated that ANXA1 is involved in miR-196a-induced cell proliferation. Furthermore, ANXA1 reversely inhibits the transcription of miR-196a via c-myc in breast cancer cells. This double negative loop between ANXA1 and miR-196a may be important in the regulation of breast cancer cell proliferation. On the other hand, the reverse expression between miR-196a and Bram1 has been found in renal cancer cells. MiR-196a directly targets 3?TUR of Bram1, and the function assay showed that Bram1 significantly inhibits cell migration in renal cancer cells. The rescue assay indicated that Bram1 is involved in the miR-196a-induced cell migration. Thus, miR-196a promotes renal cancer cell migration by directly targeting Bram1. The mechanism study suggests that Bram1 inhibits smad1/5/8 phosphorylation and MAPK pathway by directly binding to BMPR1A and EGFR. Our findings provide the new mechanism for the oncogenic role of miR-196a in breast and renal cancer cells.