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circ_AKT3 knockdown suppresses cisplatin resistance in gastric cancer
1School of Clinical Medicine, Changchun University of Chinese Medicine, Changchun, Jilin 130117, China.
Background:
Circular RNAs (circRNAs) are associated with cisplatin resistance in gastric cancer (GC). This study aims to explore the role of circRNA AKT serine/threonine kinase 3 (circ_AKT3) in the resistance of GC to cisplatin.
Methods:
42 sensitive and 23 resistant GC patients were recruited for tissue collection. The cisplatin-resistant GC cells MKN-7/DDP and HGC-27/DDP were used for in vitro study. circ_AKT3, microRNA-206 (miR-206) and protein tyrosine phosphatase non-receptor type 14 (PTPN14) levels were detected via quantitative reverse transcription real-time PCR (qPCR) and Western blot. Cisplatin resistance was assessed by detecting P-glycoprotein (P-gp) level, half maximal inhibitory concentration (IC50) of cisplatin and cell apoptosis. The target relationship between miR-206 and circ_AKT3 or PTPN14 was analyzed via dual-luciferase reporter and RNA pull-down assays. The role of circ_AKT3 in vivo was assessed using xenograft model.
Results:
circ_AKT3 level was increased, but miR-206 was declined in cisplatin-resistant GC tissues and cells. circ_AKT3 knockdown or miR-206 overexpression decreased the level of P-gp and IC50 of cisplatin and increased apoptosis of MKN-7/DDP and HGC-27/DDP cells. Additionally, circ_AKT3 targeted miR-206, and regulated cisplatin resistance by interacting with miR-206. PTPN14 was regulated by circ_AKT3 through miR-206 as a bridge. Also, circ_AKT3 knockdown decreased xenograft tumor growth.
Conclusion:
circ_AKT3 knockdown suppressed cisplatin resistance using miR-206/PTPN14 axis in cisplatin-resistant GC cells.
Insights
Circular RNAs (circRNAs) like circ_AKT3 are linked to cisplatin resistance in gastric cancer (GC). Targeting circ_AKT3 can suppress this resistance by influencing the miR-206/PTPN14 pathway in GC cells.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gastric cancer (GC) exhibits resistance to cisplatin chemotherapy.
- Circular RNAs (circRNAs) play a role in chemoresistance.
- circRNA AKT serine/threonine kinase 3 (circ_AKT3) is implicated in GC cisplatin resistance.
Purpose of the Study:
- To investigate the role of circ_AKT3 in cisplatin resistance in GC.
- To elucidate the underlying molecular mechanisms involving miR-206 and PTPN14.
Main Methods:
- Analysis of circ_AKT3 and miR-206 levels in GC patient tissues and cell lines.
- In vitro experiments using cisplatin-resistant GC cells (MKN-7/DDP, HGC-27/DDP).
- In vivo studies using a xenograft model.
- Assays included quantitative reverse transcription real-time PCR (qPCR), Western blot, dual-luciferase reporter assay, and RNA pull-down assay.
Main Results:
- circ_AKT3 levels were elevated, while miR-206 levels were decreased in cisplatin-resistant GC.
- circ_AKT3 knockdown or miR-206 overexpression reduced P-glycoprotein (P-gp) levels and cisplatin IC50, and increased apoptosis.
- circ_AKT3 directly targets miR-206, forming a regulatory axis (circ_AKT3/miR-206/PTPN14) influencing cisplatin resistance.
- circ_AKT3 knockdown inhibited tumor growth in xenograft models.
Conclusions:
- circ_AKT3 promotes cisplatin resistance in GC.
- Knockdown of circ_AKT3 suppresses cisplatin resistance via the miR-206/PTPN14 pathway.
- circ_AKT3 is a potential therapeutic target for overcoming cisplatin resistance in GC.
