Knockdown of lncRNA HIF1A-AS2 increases drug sensitivity of SCLC cells in association with autophagy.

The aim of this study was to determine the effect of lncRNA HIF1A-AS2 on autophagy-associated drug resistance in small cell lung cancer (SCLC) cells. The expression of HIF1A-AS2 was silenced by siRNA in doxorubicin-sensitive H69 and doxorubicin-resistant H69AR cells. Then, cytotoxicity, apoptosis and autophagy analyses were carried out in the normoxic and CoCl-induced hypoxic environment. The effect of HIF1A-AS2 on the expression levels of genes, which are associated with drug resistance and autophagy, was determinated by qRT-PCR analysis. The levels of MRP1, HIF-1α and Beclin-1 were analyzed by western blot method. Knockdown of HIF1A-AS2 increased doxorubicin sensitivity of SCLC cells and decreased autophagy. Knockdown of HIF1A-AS2 has also affected the expression of several genes that will increase drug sensitivity and inhibit autophagy in both cell lines. The levels of HIF-1α and Beclin-1 were decreased in both cell lines by knockdown of HIF1A-AS2. MRP1 expression was decrease in H69AR cells. In addition, CoCl-induced hypoxic environment decreased in doxorubicin sensitivity of H69 cells, and knockdown of HIF1A-AS2 reversed this effect of hypoxia. Knockdown of HIF1A-AS2 increased drug sensitivity of SCLC cells in relation to autophagy. Therefore, hypoxia-HIF1A-AS2-autophagy interaction is thought to be determinative in drug sensitivity of these cells.