title: miR-497 induces apoptosis of breast cancer cells by targeting Bcl-w.
abstract: microRNAs are a small class of non-coding RNAs with a critical role in the tumorigenesis and maintenance of breast cancer through binding to the 3'-untranslated regions of target mRNAs, which causes a block of translation and/or mRNA degradation. The purpose of this study was to investigate the expression of microRNA-497 (miR-497) as well as its potential role in human breast cancer. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to determine the expression pattern of miR-497 in breast cancer and normal breast tissues. Correlation analysis was conducted to characterize the association of miR-497 expression abnormality with pathological factors. Proliferation, cell cycle and apoptosis assays were conducted to explore the potential function of miR-497 in human MCF-7 breast cancer cells. RT-PCR and Western blot analysis were employed to validate the downstream targets of miR-497. miR-497 expression was relatively decreased in breast cancer specimens and negatively correlated with TNM stage, lymphatic metastasis, tumor size and human epidermal growth factor receptor-2 (P<0.01). On the contrary, no correlation was found with estrogen receptor, progesterone receptor and p53 status. Functional assays revealed that miR-497 suppressed cellular growth, increased the percentage of early apoptotic cells and initiated G0/G1 cell phase arrest of MCF-7 cancer cells. RT-PCR and Western blot analysis data indicated that the overexpression of miR-497 resulted in the down-regulation of Bcl-w at the mRNA and protein levels. miR-497 may serve as a tumor suppressor gene in breast cancer. The Up-regulation of miR-497 expression causes cellular growth inhibition and apoptotic enhancement, as well as G0/ G1 phase arrest, suggesting its use as a potential therapeutic target for the treatment of breast cancer in the future.
authors.affiliation: Shanghai Tenth People's Hospital;
authors.forename: Lei
authors.initials: L
authors.lastname: Shen
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Liping
authors.initials: L
authors.lastname: Xu
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Xigang
authors.initials: X
authors.lastname: Xiao
authors.forename: Junyong
authors.initials: J
authors.lastname: Zhao
authors.forename: Lin
authors.initials: L
authors.lastname: Fang