Circ_0011292 knockdown mitigates progression and drug resistance in PTX-resistant non-small-cell lung cancer cells by regulating miR-433-3p/CHEK1 axis.

Abstract

BackgroundNon‐small‐cell lung cancer (NSCLC) is one of the most common malignant tumors on earth. Circular RNAs have been disclosed to be vital regulators in the chemoresistance and development of diverse cancers, including NSCLC. Here, we attempted to explore the function of circ_0011292 in paclitaxel (PTX)‐resistant NSCLC cells.MethodsQuantitative real‐time polymerase chain reaction or western blot was performed to detect the expression of circ_0011292, microRNA‐433‐3p (miR‐433‐3p), and checkpoint kinase 1 (CHEK1). Ribonuclease R (RNase R) assay was performed to assess the stability of circ_0011292. Cell Counting Kit‐8 assay was conducted to evaluate the half maximal inhibitory concentration of PTX and cell viability. Cell proliferation was monitored by Edu incorporation and colony formation assays. Cell cycle and apoptosis were detected by flow cytometry. Transwell assay was implemented to assess cell migration and invasion. Western blot assay was utilized to determine the protein levels. Dual‐luciferase reporter assay was carried out to verify the targeted interaction between miR‐433‐3p and circ_0011292 or CHEK1. Xenograft tumor model was constructed for determining the effect of circ_0011292 in NSCLC growth in vivo.ResultsCirc_0011292 was upregulated in PTX‐resistant NSCLC tissues and cells. Circ_0011292 or CHEK1 knockdown enhanced PTX sensitivity and cell apoptosis, and repressed cell proliferation, migration, and invasion in PTX‐resistant NSCLC cells. Mechanistically, circ_0011292 was a sponge of miR‐433‐3p and miR‐433‐3p directly targeted CHEK1. Meanwhile, silencing miR‐433‐3p or overexpressing CHEK1 respectively abrogated the impacts of circ_0011292 deletion or miR‐433‐3p introduction on PTX resistance and cell progression in PTX‐resistant NSCLC cells in vitro. Moreover, circ_0011292 could positively modulate CHEK1 expression through sponging miR‐433‐3p. In addition, circ_0011292 knockdown retarded tumor growth of NSCLC in vivo.ConclusionCirc_0011292 could accelerate PTX resistance and cell malignant progression of NSCLC cells partially through the regulation of circ_0011292/miR‐433‐3p/CHEK1 axis.