Abstract
Many studies have indicated that the aberrant expression of long noncoding RNAs (lncRNAs) is responsible for drug resistance, which represents a substantial obstacle for cancer therapy. In the present study, we aimed to investigate the role of the lncRNA HOXA-AS3 in drug resistance and elucidate its underlying mechanisms in non-small-cell lung carcinoma (NSCLC) cells. The role of HOXA-AS3 in drug resistance was demonstrated by the cell counting kit-8 assay (CCK-8), ethynyldeoxyuridine (EDU) assay, and flow cytometry analysis. Tumor xenografts in nude mice were established to evaluate the antitumor effects of HOXA-AS3 knockdown in vivo. Western blotting and quantitative real-time PCR were used to evaluate protein and RNA expression. RNA pull-down assays, mass spectrometry, and RNA immunoprecipitation were performed to confirm the molecular mechanism of HOXA-AS3 in the cisplatin resistance of NSCLC cells. We found that HOXA-AS3 levels increased with cisplatin treatment and knockdown of HOXA-AS3 enhance the efficacy of cisplatin in vitro and in vivo. Mechanistic investigations showed that HOXA-AS3 conferred cisplatin resistance by down-regulating homeobox A3 (HOXA3) expression. Moreover, HOXA-AS3 was demonstrated to interact with both the mRNA and protein forms of HOXA3. In addition, HOXA3 knockdown increased cisplatin resistance and induced epithelial-mesenchymal transition (EMT). Taken together, our findings suggested that additional research into HOXA-AS3 might provide a better understanding of the mechanisms of drug resistance and promote the development of a novel and efficient strategy to treat NSCLC.