LAUSR

ABSTRACT In recent years, the problem of cancer resistance has become more and more prominent, seriously affecting treatment efficiency. Circular RNAs (circRNAs) play an important role in cell progression and cancer mechanisms. However, there is a lack of systematic studies on its function in non-small cell lung cancer (NSCLC) resistance. CircPTK2, microRNA-942 (miR-942), and Tripartite motif 16 (TRIM16) levels were detected by Real-time quantitative reverse transcriptase PCR (qRT-PCR). Extracellular acidification rate (ECAR), glucose consumption, and lactate production were assessed using the Seahorse XF96 Glycolysis Analyzer, glucose, and lactate assay kits, respectively. The protein expression was measured with the western bolt Transwell assay was used to determine migration and invasion of transfected cells. (4-5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry were applied to carry out cell proliferation and apoptosis, respectively. The relationship among circPTK2, miR-942, and TRIM16 were determined by using the dual-luciferase reporter assay and RIP assay. circPTK2 (hsa_circ_0008305) and TRIM16 were low expressed, while miR-942 was significantly highly expressed in NSCLC tissues and cell lines. Moreover, overexpression of circPTK2 remarkably inhibited cell growth, metastasis, and glycolysis in A549/CDDP and H1299/CDDP cells. Promotion of miR-942 or inhibition of TRIM16 could reverse the effects of high circPTK2 expression on cell growth, metastasis, and glycolysis in A549/CDDP and H1299/CDDP cells. CircPTK2 overexpression inhibited the growth of A549/CDDP cells in vivo. Furthermore, circPTK2 weakened CDDP resistance of NSCLC through modulating miR-942/TRIM16 axis, providing a novel sight for the treatment of NSCLC and improving the understanding of the CDDP resistance mechanism of NSCLC. Graphical Abstract