8-chloro-adenosine Inhibits Proliferation, Migration and Invasion of Breast Cancer Cells by ADAR1-Regulated miR-335-5p
Zhang Lihong, Tu Zeng, Xie Feng, Yang Shengyong*, Li Li*
The aim of this study was to investigate the effects of 8-chloro-adenosine (8-Cl-Ado) on proliferation, migration and invasion of breast cancer cells by regulating adenosine deaminases acting on RNA1 (ADAR1), and the correlation of expression between ADAR1 and miR-335-5p. After the treatment of breast cancer cells with 10 μmol/L of 8-Cl-Ado at different time points or overexpression of ADAR1 in the cells for 48 h, proliferation was examined by CCK-8 while migration and invasion were determined by Transwell, and the expression levels of ADAR1were measured by Western blot. Up-regulated miRNAs were screened by miRNA microarray and confirmed by qRT-PCR. The results showed that 8-Cl-Ado inhibited the proliferation, migration and invasion of breast cancer cells. The protein expression of ADAR1 gradually decreased in a time dependent manner. ADAR1 overexpression reduced the inhibition of proliferation, migration and invasion caused by 8-Cl-Ado. MiR-335-5p was highly expressed after 8-Cl-Ado treatment, and it was negatively regulated by ADAR1. In summary, 8-Cl-Ado inhibits proliferation, migration and invasion of breast cancer cells through down-regulating ADAR1, and its mechanism may relate to inhibition of miR-335-5p by ADAR1.