Circ-ATAD1 as Competing Endogenous RNA for miR-191-5p Forces Non-small Cell Lung Cancer Progression.

Abstract

The association of circular RNAs (circRNAs) with non-small cell lung cancer (NSCLC) has been recognized extensively. In view of this, our study particularly surveyed the underlying mechanism of circ-ATAD1 in the disease. First, an analysis of the clinical expression of circ-ATPase family AAA domain containing 1 (ATAD1) was performed, followed by further evaluation of the relationship between circ-ATAD1 expression and prognosis. Then, A549 cells were treated with single transfection or combined transfection with the plasmid vectors that interfere with circ-ATAD1 or miR-191-5p. circ-ATAD1 and miR-191-5p levels were detected by reverse transcription quantitative polymerase chain reaction to verify the transfection success. Then, cell proliferation was checked by cell count kit-8 and clonal formation test. Cell apoptosis was analyzed by flow cytometry. Cell migration and invasion were examined by wound healing assay and Transwell. Finally, the targeting of miR-191-5p to circ-ATAD1 or Forkhead Box K1 (FOXK1) was verified by bioinformation website starBase analysis and dual-luciferase reporter assay. circ-ATAD1 was expressed abundantly in tumor tissues of NSCLC patients and had a predictive value in poor prognosis. circ-ATAD1 underexpression or miR-191-5p overexpression could obstruct A549 cells to behave aggressively, while circ-ATAD1 upregulation or miR-191-5p depletion resulted in the promotion of aggressiveness of A549 cells. Interestingly, circ-ATAD1 could decoy miR-191-5p. miR-191-5p negatively regulated FOXK1 expression, and downregulating miR-191-5p or upregulating FOXK1 rescued circ-ATAD1 downregulation-mediated influences on NSCLC cells. circ-ATAD1 accelerates NSCLC progression by absorbing miR-191-5p to upregulate FOXK1 expression.