MiR-876-3p regulates cisplatin resistance and stem cell-like properties of gastric cancer cells by targeting TMED3

Abstract

Background and aim: Gastric cancer (GC), a prevalent tumor, exerts a major economic burden, and we aimed to explore miR-876-3p's effects on GC and related mechanisms.

Methods: Cell viability was analyzed via CCK-8 and colony formation assay. Stem cell-like properties were examined via spheroid colony formation assay. mRNA abundance of key genes was analyzed via quantitative polymerase chain reaction. Protein level of TMED3 and stem cell markers was examined by western blot. TargetScan, luciferase, and biotin-miRNA pulldown assay were used to identify miR-876-3p's target.

Results: MiR-876-3p was downregulated in GC, and its mRNA level had negative relationship with cisplatin resistance of GC. Moreover, decreased miR-876-3p expression level suggested poor prognosis of GC patients. MiR-876-3p inhibited drug resistance of cisplatin-resistant cell line SGC-7901/DDP and MKN-45/DDP, as shown by decreased cell viability, IC₅₀ , and colony formation ability. MiR-876-3p inhibited stem cell-like features and downregulated the expressions of Sox-2, Oct-4, CD133, and CD44 in GC cells. Luciferase and biotin-miRNA pulldown assay confirmed that TMED3 was miR-876-3p's direct target. TMED3 siRNA inhibited miR-876-3p's effects on cisplatin resistance and stem cell-like features of SGC-7901/DDP cells.

Conclusion: MiR-876-3p enhanced cisplatin sensitivity and restricted stem cell-like features of GC through targeting TMED3.

Keywords: TMED3; anti-tumor; cisplatin resistance; gastric cancer; miR-876-3p.