Abstract
Increasing evidence has revealed the contributions of long noncoding RNAs (lncRNAs) in the modulation of drug resistance in gastric cancer. In the present study, we explored the role of a novel lncRNA, RP11-874J12.4, in regulating chemoresistance in gastric cancer and determined the underlying molecular mechanisms. We observed that compared with normal controls, human gastric cancer tissues and cell lines, including MKN-45 and AGS cells, expressed higher RP11-874J12.4 levels. RP11-874J12.4 knockdown sensitized MKN-45 and AGS cells to docetaxel and cisplatin in terms of cell viability and apoptosis rate. In addition, RP11-874J12.4 was found to be a competing endogenous RNA that sponged microRNA (miR)-3972, which showed significantly reduced expression in human gastric cancer tissues and cell lines. Furthermore, signal sequence receptor subunit 2 (SSR2) was identified as a downstream target of miR-3972, and the miR-3972/SSR2 axis was found to regulate chemoresistance in MKN-45 and AGS cells. SSR2 downregulation further sensitized gastric cancer cells with RP11-874J12.4 knockdown to chemotherapeutic drugs via enhanced apoptosis, which was evidenced by significantly upregulated expressions of cleaved caspase-3, cleaved caspase-9, and Bax and downregulated expression of Bcl-2. Furthermore, RP11-874J12.4 knockdown markedly inhibited the growth of xenograft MKN-45 cells in nude mice, which was associated with an increased expression of miR-3972 and decreased expression of SSR2 in tumors. Therefore, the RP11-874J12.4/miR-3972/SSR2 axis plays important roles in the regulation of chemoresistance in MKN-45 and AGS cells and may serve as a target for the diagnosis and treatment of human gastric cancer.