Knockdown of circ-PVT1 inhibits the progression of lung adenocarcinoma and enhances the sensitivity to cisplatin via the miR-429/FOXK1 signaling axis

Lung cancer is one of the most prevalent cancers in China, and its incidence and morbidity remain high due to various independent factors. Lung adenocarcinoma (ADC) is the most common type of non-small cell lung carcinoma. Circular RNA plasmacytoma variant translocation 1 (circ-PVT1) plays an oncogenic role in various types of cancer, but the specific role of circ-PVT1 in lung ADC has not yet been reported. In the present study, circ-PVT1 was knocked down in A549 cells and the cell viability, proliferation, migration and invasion were measured via MTT, colony formation, wound healing and Transwell assays, respectively. Then, the cell viability of A549 cells with circ-PVT1-knockdown or -overexpression was detected after exposure to cisplatin (DDP). After confirming the associations among circ-PVT1, microRNA (miR)-429 and forkhead box k1 (FOXK1) using various tools and assays, the cellular functions of A549 cells treated with combined short hairpin (sh)RNA-circ-PVT1 and miR-429 inhibitor/pcDNA3.1-FOXK1 were tested again. The expression of circ-PVT1 was found to be increased in lung ADC cells, and shRNA-circ-PVT1 led to decreased cell viability, proliferation, migration and invasion. The expression of circ-PVT1 was higher in A549/DDP cells than that in A549 cells, and the activity of caspase-3 was also activated by DDP in A549/DDP cells transfected with shRNA-circ-PVT1, whereas it was inactivated by DDP in A549 cells transfected with circ-PVT1 overexpression plasmid. Furthermore, the decreased cell viability, proliferation, invasion and migration induced by shRNA-circ-PVT1 could be abated by transfection with miR-429 inhibitor and pcDNA3.1-FOXK1. In conclusion, interference of circ-PVT1 inhibits the progression of lung ADC and enhances its sensitivity to DDP via miR-429/FOXK1, which may provide a theoretical basis for the use of novel targets in the treatment of lung ADC.