Circ_0074027 contributes to the progression of non-small cell lung cancer via microRNA-362-3p/clathrin heavy chain axis

Abstract

Circular RNAs are involved in the occurrence and development of different types of cancers. We aimed to illustrate the expression profile and mechanism of circ_0074027 in non-small cell lung cancer (NSCLC). Quantitative real-time PCR was employed to detect the expression of circ_0074027, paired like homeodomain 1 (PITX1) mRNA (mPITX1) and microRNA-362-3p (miR-362-3p). Western blot assay was utilized to measure the levels of clathrin heavy chain (CLTC), cyclin D1, BCL2-associated X, apoptosis regulator Bax (Bax), vimentin and matrix metallopeptidase 9. The clonogenicity, apoptosis and metastasis of NSCLC cells were examined by colony formation assay, flow cytometry and transwell migration and invasion assays. The target relationship between miR-362-3p and circ_0074027 or CLTC was predicted by starBase website and was validated by dual-luciferase reporter assay. Murine xenograft assay was applied to explore the function of circ_0074027 in vivo. We found that The enrichment of circ_0074027 and CLTC protein was elevated, and a significant reduction in the expression of miR-362-3p was observed in NSCLC tissues and cells relative to adjacent normal tissues and human bronchial epithelial cells 16HBE. Circ_0074027 possessed a stable circular structure. Circ_0074027 and CLTC could accelerate the colony formation and metastasis and suppress the apoptosis of NSCLC cells. Circ_0074027/miR-362-3p/CLTC axis was first found to regulate the malignance of NSCLC cells. The biological influence caused by circ_0074027 depletion on NSCLC cells was alleviated by the accumulation of CLTC. Circ_0074027 acted as an oncogene to promote the growth of NSCLC tumors in vivo. In conclusion, Circ_0074027 contributed to the progression of NSCLC through promoting the proliferation and motility while hampering the apoptosis of NSCLC cells via miR-362-3p/CLTC axis.