MiR-338-3p attenuates oxaliplatin resistance in gastric cancer cells via targeting thrombospondin-1

Abstract

IntroductionOxaliplatin resistance (OR) as a poor prognostic factor is closely associated with gastric cancer (GC) recurrence and metastasis. The present study aimed to explore the molecular mechanism underlying oxaliplatin-based chemotherapy resistance of GC.Material and methodsTwo acquired OR strains (BGC-823-OR and MGC-803-OR) were generated by long-term oxaliplatin induction. Cell viability, apoptosis, migration and invasion were evaluated using CCK-8, TUNEL staining and transwell assay, respectively. THBS1 as a direct target of miR-338-3p was validated using the bioinformatics algorithm and luciferase reporter assay. qRT-PCR and western blotting were used to measure gene and protein expression, respectively.ResultsmiR-338-3p was significantly down-regulated, and THBS1 protein level was significantly up-regulated in BGC-823-OR and MGC-803-OR cells compared with parental cell lines. Overexpression of miR-338-3p elevated oxaliplatin sensitivity in BGC-823-OR and MGC-803-OR cells. In addition, we revealed that THBS1 was a direct target of miR-338-3p. Overexpression of miR-338-3p or silence of THBS1 inhibited growth, migration and invasion and promoted apoptosis in BGC-823-OR and MGC-803-OR cells.ConclusionsmiR-338-3p appeared to obtund oxaliplatin-based chemotherapy resistance of GC cells by repression of THBS1. The miR-338-3p/ THBS1 signaling axis might be a prospective therapeutic target to mitigate chemotherapy resistance in GC.