circ_0006528 promotes nonsmall cell lung cancer progression by sponging miR-892a and regulating NRAS expression.

Micro-RNAs play essential roles in developing and progressing nonsmall cell lung cancer (NSCLC) and drug resistance. Nevertheless, the functions and mechanisms are partly explored. Therefore, the present study analyzes the effect of circ_0006528 and the mechanism of regulation of NSCLC cell progression by sponging miR-892a to regulate neuroblastoma rat sarcoma viral oncogene (NRAS) expression. Initially, circ_0006528 is identified using divergent primers-based PCR and RNase R exonuclease treatments. After administration of the designed circ_0006528-specific siRNA, the RT-qPCR analysis is used to determine the interference efficiency of siRNA. At the same time, cell growth, invasion, and migration are assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT), Transwell, and scratch assays in the NSCLC cell lines (secretory pathway Ca2+-ATPase isoform 1 [SPCA-1] and A549) in vitro, respectively. Further, miR-892a inhibitor is added to the cells for functional recovery assay. Finally, the xenograft mouse model is constructed to explore the effect of circ_0006528 on tumor growth in vivo. The RT-qPCR analysis in 66 pairs of NSCLC cancer and noncancerous tissues revealed that circ_0006528 is highly expressed in NSCLC patient tissues. The RNase R experiments revealed that HSA_circ_0006528 is unaffected by RNase R exonuclease. MTT assay showed that knockdown of hsa_circ_0006528 by siRNA significantly decreased cell proliferation and viability in A549 and SPCA-1 cells. The luciferase reporter assay showed direct binding of hsa_circ_0006528 to miR-892a, and miR-892a targets binding NRAS. In addition, the miR-892a inhibitor terminated the hsa_circ_0006528 siRNA, triggering inhibition of proliferation, invasion, and migration of NSCLC cells. In summary, the study revealed that the knockout of hsa_circ_0006528 downregulation of NRAS expression by sponging miR-892a inhibited NSCLC cell growth and invasion.