Up-regulation of miR-506 inhibits cell growth and disrupt the cell cycle by targeting YAP in breast cancer cells

Int J Clin Exp Med. 2015 Aug 15;8(8):12018-27. eCollection 2015.


MicroRNAs (miRNAs) are a small class of non-coding RNAs that are extensively deregulated in various cancers. They can act as either oncogenes or tumor suppressor genes in human cancer. The purpose of this study was to investigate the crucial role of miR-506 in breast cancer and to validate whether miR-506 could regulate proliferation of breast cancer cells by targeting YAP (Yes-associated protein) gene. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to quantify the expression levels of miR-506 in breast cancer and adjacent non-cancerous breast tissues. To characterize the miR-506 function, MTT assays, colony formation assays, cell migration assays, cell invasion assays and cell cycle assays were used. Finally, luciferase reporter assays were performed to validate the regulation of a putative target of miR-506, in corroboration with western blot assays. We found that expression of miR-506 was commonly down-regulated in breast cancer cells and breast cancer specimens when compared with that in non-malignant breast epithelial cells and adjacent normal tissues. Up-regulation of miR-506 inhibited cellular proliferation, migration and invasion as well as disrupt the cell cycle of breast cancer cells. Luciferase assays revealed that miR-506 directly bound to the 3'-untranslated region (3'-UTR) of YAP. Western blot analysis verified that miR-506 regulated the expression of YAP at the protein levels. These findings suggest that miR-506 exerts as a tumor suppressor in breast cancer and up-regulation of miR-506 expression inhibits cellular growth, cell migration and invasion as well as disrupt the cell cycle by targeting YAP. Our study demonstrates that the miR-506/YAP axis may help us better understand the molecular mechanisms of breast cancer progression.

Keywords: MiR-506; YAP; breast cancer.