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

Güçlü E., Eroğlu Güneş C., Kurar E., Vural H.

Medical Oncology, vol.38, no.9, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 38 Issue: 9
  • Publication Date: 2021
  • Doi Number: 10.1007/s12032-021-01562-2
  • Journal Name: Medical Oncology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CINAHL, EMBASE, MEDLINE
  • Keywords: Autophagy, Drug resistance, HIF1A-AS2, SCLC
  • Yozgat Bozok University Affiliated: No

Abstract

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 CoCl2-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, CoCl2-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.