Silencing ARHGAP9 correlates with the risk of breast cancer and inhibits the proliferation, migration, and invasion of breast cancer

沉默 ARHGAP9 与乳腺癌风险相关并抑制乳腺癌的增殖、迁移和侵袭

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作者:Tianyi Wang, Minwen Ha

Abstract

Breast cancer (BC) is one of the most common malignant tumors in women, and screening relevant genes and markers that are involved in BC tumor genesis and progression is of great value. We previously found that messenger RNA expression of ARHGAP9 was high in BC tissue, but it is unclear whether ARHGAP9 participates in the progression of human BC. In this study, we found that ARHGAP9 expression was correlated with poor patient survival, American Joint Committee on Cancer clinical staging, tumor size, and tumor differentiation. MCF-7 and MDA-MB-231 cells exhibited higher expression of ARHGAP9 than other human BC cell lines (HCC1937, MDA-MB-453, ZR-75-1, and Hs 578T). Knockdown of ARHGAP9 in human BC cells markedly reduced the cell proliferation, migration, and invasive ability of MCF-7 and MDA-MB-231 cells. Furthermore, small interfering RNA (siRNA) of ARHGAP9 also induced G0-G1 cell cycle arrest and apoptosis in MCF-7 and MDA-MB-231 cells. Expressions of cell cycle markers (CDK2 and CCNB1) and invasion-related protein (RhoC and MTA1) were downregulated in siRNA-ARHGAP9-transfected cells. siRNA of ARHGAP9 also inhibited the phosphorylation of mitogen-activated protein kinases in BC cells. In conclusion, the abnormal expression of ARHGAP9 may correlate with the genesis, development, and diagnosis of BC.

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