A Cytoplasm-Enriched circRNA circ-MYBL2 is Downregulated in Non-Small Cell Lung Cancer and Sponges Oncogenic miR-28 to Regulate Cancer Cell Proliferation and Apoptosis

Background: Recent studies have reported different roles of circRNA circ-MYBL2 in different cancers. However, the involvement of circ-MYBL2 in non-small cell lung cancer (NSCLC) is unknown. This study was carried out to explore the role of circ-MYBL2 in NSCLC.

Methods: The expression of circ-MYBL2 and miR-28 was detected by RT-qPCR. A 5-year follow-up study was performed for survival analysis. Nuclear fractionation assay was used for subcellular localization analysis. RNA pull-down assay was performed to detect the interaction between circ-MYBL2 and miR-28. The role of circ-MYBL2 and miR-28 in regulating the expression of each other was evaluated by overexpression assay. BrdU incorporation assay and cell apoptosis assay were performed to investigate the role of circ-MYBL2 and miR-28 in cell proliferation and apoptosis.

Results: NSCLC tissues exhibited significantly higher expression levels of miR-28 and lower expression levels of circ-MYBL2. Close correlations between circ-MYBL2 and miR-28 and patients' survival were observed. Circ-MYBL2, which was found to be mainly enriched in cytoplasm, directly interacted with miR-28. Although circ-MYBL2 and miR-28 showed no regulatory role in the expression of each other, circ-MYBL2 suppressed the effects of miR-28 on cell proliferation and apoptosis.

Conclusion: Circ-MYBL2 is enriched in cytoplasm, and it sponges oncogenic miR-28 to suppress cancer cell proliferation in NSCLC and promote cell apoptosis.