Tumor-suppressive microRNA-let-7a inhibits cell proliferation via targeting of E2F2 in osteosarcoma cells.

Abstract

MicroRNAs (miRNAs) regulate cell proliferation and differentiation by silencing gene expression at the post-transcriptional level; moreover, by binding to the complementary sequences within mRNAs in cancer cells, these small non-coding RNA molecules can function as tumor suppressors or oncogenes. Recently, the dysregulation of miRNA expression has been found to be associated with increased tumorigenicity and poor prognosis in several cancer types, including osteosarcoma (OS). To identify potential oncogenic factors in OS, we analyzed changes in the expression profile of miRNAs and its downstream mRNAs in five OS cell lines and human mesenchymal stem cells (hMSCs) by a microarray-based approach. The expression of an miRNA-let‑7a was significantly downregulated and E2F2 was significantly upregulated in all tested OS cells compared with hMSCs. When let-7a was transfected into OS cell lines, the expression of E2F2 in the cells was greatly suppressed, suggesting that E2F2 is a target of miRNA-let-7a in OS cells. The transfection of let-7a further inhibited cell cycle progression and proliferation of OS cells. In addition, let-7a overexpression in OS cells significantly suppressed the tumor growth invivo. The present study demonstrates the novel mechanism that regulates E2F2 expression via miRNA-let-7a in OS cells. Because E2F2 is pivotal in promoting cell growth through the regulation of several genes, our results might facilitate the development of new therapeutic targets for the treatment of OS.