CircMIIP Contributes to Non-Small Cell Lung Cancer Progression by Binding miR-766-5p to Upregulate FAM83A Expression

Background: Circular RNA migration and invasion inhibitory protein (circMIIP) is reported to be upregulated in non-small cell lung cancer (NSCLC) tissues compared with normal tissues. However, the role and working mechanism of circMIIP in NSCLC progression remain largely unclear.

Methods: Cell proliferation ability was analyzed by colony formation assay, cell counting kit-8 (CCK-8) assay, and 5-ethynyl-2'-deoxyuridine assay. Cell apoptosis was assessed by flow cytometry. Transwell assays were performed to analyze the migration and invasion abilities of NSCLC cells. The interaction between microRNA-766-5p (miR-766-5p) and circMIIP or family with sequence similarity 83A (FAM83A) was validated by dual-luciferase reporter assay and RNA immunoprecipitation assay. Xenograft tumor model was established to analyze the role of circMIIP on tumor growth in vivo.

Results: CircMIIP was highly expressed in NSCLC tissues and cell lines. CircMIIP knockdown restrained the proliferation, migration and invasion and induced the apoptosis of NSCLC cells. CircMIIP acted as a molecular sponge for miR-766-5p, and circMIIP silencing-mediated anti-tumor effects were largely overturned by the knockdown of miR-766-5p in NSCLC cells. miR-766-5p interacted with the 3' untranslated region (3'UTR) of FAM83A, and FAM83A overexpression largely reversed miR-766-5p accumulation-induced anti-tumor effects in NSCLC cells. CircMIIP competitively bound to miR-766-5p to elevate the expression of FAM83A in NSCLC cells. CircMIIP knockdown significantly restrained xenograft tumor growth in vivo.

Conclusion: CircMIIP promoted cell proliferation, migration and invasion and suppressed cell apoptosis in NSCLC cells through mediating miR-766-5p/FAM83A axis.