hsa_circ_0058357 acts as a ceRNA to promote non-small cell lung cancer progression via the hsa-miR-24-3p/AVL9 axis

Abstract

Abnormal circular RNAs (circRNAs) are associ- ated with biological processes in cancer; however, the function of circRNAs remains largely unknown in non-small cell lung cancer (NSCLC). The present study aimed to investigate the role of hsa_circ_0058357 on the progression of NSCLC. Cell proliferation, migration and apoptosis were determined using Cell Counting Kit-8, Transwell and flow cytometry assays, respectively. Gene [circRNA and microRNA (miR)] and protein expression levels were determined via reverse transcription-quantitative PCR and immunoblotting. A lucif- erase assay was employed to detect the binding of miR-24-3p with AVL9 cell migration associated (AVL9), while a cancer xenograft model was established to evaluate cancer growth in vivo. The results demonstrated that hsa_circ_0058357 was highly expressed in human NSCLC tissues and NSCLC cells compared with para-cancerous tissues and human bronchial epithelial (HBE) cells, respectively. Knockdown of hsa_circ_0058357significantlysuppressedcellviability,migra- tion and tumor growth, while it promoted apoptosis in NSCLC cells. As a competing endogenous RNA, hsa_circ_0058357 knockdown contributed to the increase of miR-24-3p expres- sion in NSCLC cells. Of note, overexpression of miR-24-3p markedly abolished the exogenous hsa_circ_0058357-induced excessive proliferation, migration and apoptosis resistance of NSCLC cells. Mechanistically, as a signaling molecule in late secretory pathway, AVL9 was also expressed at a high level in NSCLC tissues and cells, which could be directly suppressed by miR-24-3p. In the tumor tissues, along with growth inhibition, hsa_circ_0058357 knockdown also mediated the elevation of miR-24-3p and the reduction of AVL9. Thus, it was suggested that hsa_circ_0058357 may be a crucial regula- tion factor in NSCLC by sponging hsa-miR-24-3p, leading to a decrease in miR-24-3p expression, and subsequent increase in AVL9 expression. Therefore, hsa_circ_0058357 may serve as a potential target for diagnosis and gene therapy for NSCLC.