CircPKM2 aggravates the progression of non-small cell lung cancer by regulating MTDH via miR-1298-5p.

Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with high morbidity and mortality. The role of dysregulated circular RNAs (circRNAs) in human diseases are receiving more and more attention. In this study, we focused on the role and mechanism of circPKM2 in the progression of NSCLC.
Methods: The expression levels of circPKM2, microRNA-1298-5p (miR-1298-5p) and metadherin (MTDH) in NSCLC were measured by real-time quantitative PCR (qRT-PCR) or Western blot. Cell counting kit-8 (CCK-8), colony formation, 5-ethynyl-2'-deoxyuridine (EdU) staining, flow cytometry, transwell and tube formation assays were conducted to evaluate the effects of circPKM2 on malignant phenotypes of NSCLC. Western blot was used to measure related marker protein levels.
Results: CircPKM2 and MTDH were highly expressed in NSCLC tissues and cells, while miR-1298-5p was downregulated. CircPKM2 knockdown effectively suppressed cell proliferation, migration, invasion and tube formation whereas induced apoptosis in vitro. CircPKM2 had a potential targeting site with miR-1298-5p and negatively regulated the expression of miR-1298-5p. MiR-1298-5p inhibitor reversed the effect of circPKM2 knockdown on the progression of NSCLC. CircPKM2 induced MTDH expression via sponging miR-1298-5p to promote the progression of NSCLC. MiR-1298-5p directly targeted MTDH, and the addition of MTDH partially attenuated the inhibition of miR-1298-5p on the progression of NSCLC. In addition, the downregulation of circPKM2 significantly slowed down the growth of xenograft tumors in vivo.
Conclusion: Our findings demonstrated that circPKM2 mediated NSCLC progression via regulating miR-1298-5p/MTDH axis, providing a novel therapeutic target for NSCLC.
(© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)