CircRNA WHSC1 promotes non-small cell lung cancer progression via sponging microRNA-296-3p and up-regulating expression of AKT serine/threonine kinase 3

Background Lung cancer is the most commonly diagnosed cancer and leading cause of cancer death, with 80%-85% of non-small cell lung cancer (NSCLC). Circular RNAs (circRNAs) have been shown to be promising early diagnostic and therapeutic molecular biomarkers for NSCLC. However, biological role and regulatory mechanism of circRNA WHSC1 (circWHSC1) in NSCLC are unknown. Therefore, we aim to explore the function and mechanism of circWHSC1 in NSCLC oncogenesis and progression. Methods qRT-PCR was used for circWHSC1 level evaluation; Kaplan-Meier was used for survival analysis; bioinformatics, dual-luciferase activity, and RNA pull-down were used for evaluating competing endogenous RNA (ceRNA) network; cell viability, colony formation, apoptosis, migration, and invasion were used for cell function analysis; function gain and loss with rescue experiments were used for exploring mechanism of circWHSC1 in NSCLC development. Results Significantly up-regulated circWHSC1 and down-regulated microRNA-296-3p (miR-296-3p) were identified in NSCLC tissues and cells. Up-regulated circWHSC1 was associated with poor prognosis in NSCLC patients. MiR-296-3p was sponged by circWHSC1, and AKT serine/threonine kinase 3 (AKT3) was target of miR-296-3p; meanwhile, miR-296-3p over-expression significantly down-regulated AKT3 expression, and co-transfecting anti-miR-296-3p rescued circWHSC1 silence caused AKT3 down-regulation. CircWHSC1 silence significantly inhibited colony formation, viability, invasion, and migration, while increased NSCLC cell apoptosis, which were partially rescued by anti-miR-296-3p. Conclusion CircWHSC1 is an independent indicator of poor prognosis in NSCLC patients, and functions as a ceRNA of miR-296-3p to up-regulate AKT3, consequently promotes NSCLC cell growth and metastasis. Targeting circWHSC1 might be a prospective strategy for diagnosis, therapeutics, and prognosis of NSCLC.

Automated summary

This study found that circWHSC1 is significantly up-regulated in NSCLC patients and is associated with poor prognosis. CircWHSC1 acts as a ceRNA of miR-296-3p to up-regulate AKT3 and promote NSCLC cell growth and metastasis. Targeting circWHSC1 might be a potential strategy for NSCLC diagnosis, therapeutics, and prognosis.