Large intergenic non-coding RNA-ROR reverses Gemcitabine-induced autophagy and apoptosis in breast cancer cells

The purpose of this study was to elucidate the potential role of long intergenic non-protein coding RNA, regulator of reprogramming (linc-ROR) in gemcitabine (Gem)-induced autophagy and apoptosis in breast cancer cells. MDA-MB-231 cells were treated with short hairpin RNA (shRNA) to knockdown Linc-ROR expression in the presence of Gem. Gem treatment alone decreased cell survival and increased both apoptosis and autophagy. Gem treatment also increased the expression of LC3-II, Beclin 1, NOTCH1 and Bcl-2, but decreased expression of p62 and p53. Untreated MDA-MB-231 cell lines strongly expressed linc-ROR, but linc-ROR knockdown decreased cell viability and expression of p62 and p53 while increasing apoptosis. Linc-ROR knockdown also increased LC3-II/beta-actin, Beclin 1, NOTCH1, and Bcl-2 expression, as well as the number of autophagic vesicles in MDA-MB-231 cells. Linc-ROR negatively regulated miR-34a expression by inhibiting histone H3 acetylation in the miR-34a promoter. We conclude that linc-ROR suppresses Gem-induced autophagy and apoptosis in breast cancer cells by silencing miR-34a expression.