Published online Feb 14, 2021. doi: 10.3748/wjg.v27.i6.487
Peer-review started: December 6, 2020
First decision: December 17, 2020
Revised: December 21, 2020
Accepted: January 7, 2021
Article in press: January 7, 2021
Published online: February 14, 2021
Processing time: 60 Days and 21.3 Hours
Gastric cancer (GC) is a common malignant tumor and causes a high incidence of cancer-associated death. Cisplatin (DDP)-based chemotherapy is the main therapy for clinical GC treatment, but the mechanism of chemotherapy resistance is still poorly understood, which is a severe clinical challenge. CircRNAs have been identified to play a vital role in regulating the chemoresistance of gastric cancer cells. The development process of GC chemotherapy resistance is not well-understood. In addition, it is well known that circRNAs and miRNAs are involved in chemotherapy resistance of GC cells. However, the role of circVAPA and miR-125b-5p in regulating the chemotherapy resistance of GC cells has not been reported yet.
To investigate the impact of circVAPA on chemotherapy resistance during the progression of GC.
We collected the clinical GC tissue samples (n = 50) and the adjacent normal tissues (n = 50) and analyzed the effect of circVAPA on GC progression and chemotherapy resistance.
The role of circVAPA in chemotherapy resistance and GC progression was analyzed by transwell assay, MTT assay, colony formation assay, healing assay, and wound flow cytometry analysis in GC cells and DDP resistant GC cell lines, and in vivo tumorigenicity analysis in nude mice. The mechanism was investigated by quantitative real-time PCR, luciferase reporter assay, and Western blot analysis.
CircVAPA depletion inhibited proliferation, migration, and invasion and increased apoptosis of GC cells. CircVAPA knockdown reduced tumor growth of GC cells in vivo. CircVAPA promoted the chemotherapy resistance of GC cells. We found that circVAPA targeted miR-125b-5p and miR-125b-5p to STAT3 in GC cells. MiR-125b-5p inhibitor rescued the depletion of circVAPA and enhanced the inhibitory effect of DDP on GC cells, while STAT3 knockdown prevented the proliferation of DDP-treated SGC7901/DDP cells induced by circVAPA overexpression. Depletion of STAT3 and miR-125b-5p inhibitor reversed circVAPA depletion-induced GC cell apoptosis.
CircVAPA promotes chemotherapy resistance and the malignant progression of GC cells by modulating miR-125b-5p/STAT3 signaling. CircVAPA and miR-125b-5p may be considered as potential targets for GC therapy.
CircRNA circVAPA promotes chemotherapy drug resistance in the progression of gastric cancer by regulating the miR-125b-5p/STAT3 axis.