Down-regulation of CASC2 contributes to cisplatin resistance in gastric cancer by sponging miR-19a

Abstract

Increasing evidence suggests the involvement of long non-coding RNAs (lncRNAs) in chemoresistance of cancer treatment. However, their function and molecular mechanisms in gastric cancer chemoresistance are still not well elucidated. In the present study, we investigate the functional role of lncRNA cancer susceptibility candidate 2 (CASC2) in cisplatin (DDP) resistance of gastric cancer and discover the underlying molecular mechanism. Results revealed that CASC2 was decreased in DDP-resistant gastric cancer tissues and cells. Gastric cancer patients with low CASC2 expression levels had a poor prognosis. CASC2 overexpression enhanced DDP sensitivity of BGC823/DDP and SGC7901/DDP cells. Conversely, CASC2 knockdown weakened the response of BGC823 and SGC7901 to DPP. Moreover, CASC2 could function as a miR-19a sponge. miR-19a inhibition could overcome DDP resistance in BGC823/DDP and SGC7901/DDP cells, while miR-19a overexpression led to DDP resistance in BGC823 and SGC7901 cells. Notably, miR-19a overexpression counteracted CASC2 up-regulation-mediated enhancement in DDP sensitivity of BGC823/DDP and SGC7901/DDP cells. On the contrary, the inhibitory effect of CASC2 knockdown on the sensitivity of BGC823 and SGC7901 cells to DDP was reversed by miR-19a inhibition. In summary, CASC2 overexpression overcame DDP resistance in gastric cancer by sponging miR-19a, providing a novel therapeutic target for gastric cancer chemoresistance.

Keywords: Cisplatin; Gastric cancer; lncRNA cancer susceptibility candidate 2; miR-19a.