Mir-328 Targets Histone H2ax And Regulates Lung Cancer Cells Apoptosis

Increasing reports indicate that microRNAs play a key role in cell growth, differentiation, and apoptosis. In this study, we describe how the regulation of miRNA-328 (miR-328), which increases in cancer cells, is involved in the apoptosis of lung cancer cells (A549 and NCI-H1650). Expression analysis has verified that the level of miR-328 is significantly decreased in apoptotic A549 and NCI-H1650 cells. Furthermore, overexpression of miR-328 in lung cancer cells inhibits etoposide-induced cellular apoptosis. Additionally, we identified that histone H2AX is a downstream target of miR-328, which can bind directly to the 3'-untranslated region (3'-UTR) of H2AX, subsequently downregulating both the mRNA and protein levels of H2AX. The results from co-expression demonstrated that overexpression of H2AX which lacked 3'-UTR in A549 and NCI-H1650 cells partially reduces the effect of miR-328 on cell apoptosis. Taken together, our results illuminate that miR-328 functions as an apoptosis silencer to regulate lung cancer cell apoptosis through targeting histone H2AX and may become a critical therapeutic target in lung cancer.