miR-96 promotes tumor proliferation and invasion by targeting RECK in breast cancer

Junfeng Zhang, Xiangjie Kong, Jia Li, Qifeng Luo, Xiaoyu Li, Lei Shen, Lei Chen, Lin Fang
Oncology Reports 2014, 31 (3): 1357-63
microRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression in diverse biological processes. The aim of the present study was to investigate the expression pattern of miR-96 in breast cancer and its biological role in tumor progression. The expression levels of miR-96 were analyzed in 38 breast cancer specimens and 6 breast cancer cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The effect of miR-96 on proliferation was evaluated by MTT assays, and cell migration and invasion were evaluated by transwell assays in MDA-MB-231 human breast cancer cells. Luciferase reporter assays were performed to validate the regulation of a putative target of miR-96. The effects of modulating miR-96 on endogenous levels of this potential target were subsequently confirmed via qRT-PCR and western blot analysis. We found that expression of miR-96 was commonly upregulated in breast cancer cells and breast cancer specimens when compared with that in non-malignant breast epithelial cells and adjacent normal tissues. Ectopic expression of miR-96 promoted cellular proliferation, migration and invasion of breast cancer cells, whereas inhibition of miR-96 suppressed those functions. Luciferase assays revealed that miR-96 directly bound to the 3'-untranslated region (3'-UTR) of RECK. qRT-PCR and western blot analysis confirmed that miR-96 regulated the expression of RECK both at the mRNA and protein levels. Knockdown of RECK expression in MDA-MB-231 cells by siRNA significantly promoted cell proliferation, migration and invasion. Collectively, miR-96 was significantly upregulated in breast cancer. our data also delineate the molecular pathway by which miR-96 promotes breast cancer proliferation, migration and invasion. Our findings may have important implications for the treatment of breast cancer.

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