MiR-643 Functions as a Potential Tumor Suppressor in Gastric Cancer by Inhibiting Cell Proliferation and Invasion Targeting TXNDC9.

Objective: Gastric cancer is one of the most common gastrointestinal malignancies. miRNAs (microRNAs) have been reported to play a pivotal role in the tumorigenesis of gastric cancer. However, the role of miR-643 in gastric cancer is not fully understood.

Methods: The expression of miR-643 in gastric cancer cell lines was detected by qRT-PCR (quantitative reverse transcription PCR). Cell viability, apoptosis, migration, and invasion were assessed using the Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and wound scratch and Transwell assays, respectively. The target gene of miR-643 was predicted by bioinformatics analysis and validated using luciferase reporter assay.

Results: The expression level of miR-643 in gastric cancer cell lines was lower than in the normal gastric epithelium cell line (GES-1). Overexpression of miR-643 inhibited cell viability and colony formation but promoted cell apoptosis in gastric cancer. Transwell invasion assay and scratch assay evidenced that miR-643 overexpression inhibited gastric cancer cell migration and invasion. Bioinformatics analysis revealed that miR-643 could directly target TXNDC9 (Thioredoxin domain containing 9), and luciferase reporter assay validated this result. Further analysis showed that miR-643 mimics caused a significant reduction of TXNDC9 in gastric cancer cells. Moreover, TXNDC9 overexpression reversed the effects of miR-643 mimics on gastric cancer cell viability, invasion, and migration.

Conclusion: miR-643 functions as a potential tumor suppressor in gastric cancer by inhibiting cell viability, colony formation, migration, and invasion via targeting TXNDC9, which provides a novel target for the diagnostic treatment of gastric cancer.