AB50. miR-503 modulates drug resistance of human gastric cancer cell lines by targeting BCL2

Purpose: MicroRNAs (miRNAs) are short non-coding RNA molecules, which post-transcriptionally regulate genes expression and play crucial roles in diverse biological processes. Recent studies have shown that dysregulation of miRNAs might modulate the resistance of cancer cells against anti-cancer drugs, yet the modulation mechanism has not been fully understood. We aimed to investigate the possible roles of miRNAs in the development of drug resistance in human gastric cancer cell lines.

Methods: miRNA Quantitative real-time PCR was used to detect the different miRNAs expression level between drug resistant and parental cancer cells. MTT [3- (4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay was used to test phenotype changes in drug resistance of cancer cells via over or down regulation of miRNAs. Dual-luciferase activity assay was used to verify the target genes of miRNAs. Western blot analysis and apoptosis assay were employed to elucidate the mechanism of miRNAs on modulating drug resistance of cancer cells.

Results: miR-503 was downregulated while BCL2 was upregulated in both SGC7901/VCR (vincristine) and SGC7901/CDDP (cisplatin) cells, compared with the parental SGC7901 cells, respectively. Overexpression of miR-503 sensitized SGC7901/VCR and SGC7901/CDDP cells to anticancer drugs, respectively. BCL2 3'-UTR reporters constructed in drug resistant cells suggested that BCL2 was the direct target gene of the miR-503. Enforced miR-503 expression decreased BCL2 protein level and sensitized both drug resistant cells to VCR-induced and CDDP-induced apoptosis, respectively.

Conclusions: Our findings suggest that miR-503 could play a role in the development of drug resistance in gastric cancer cell lines at least in part by modulation of apoptosis via targeting BCL2.

Keywords: miR-503; drug resistance; BCL2; gastric cancer