非小细胞肺癌（NSCLC）是最常见的肺癌类型，具有较高的发病率和死亡率。异常调节的环状RNA（circRNAs）在人类疾病中的作用越来越受关注。本研究重点研究circPKM2在NSCLC进展中的作用和机制。通过实时定量PCR（qRT-PCR）或Western印迹法测量NSCLC中circPKM2、microRNA-1298-5p（miR-1298-5p）和metadherin（MTDH）的表达水平。利用细胞计数试剂盒-8（CCK-8）、克隆形成、5-乙炔基-2'-脱氧尿苷（EdU）染色、流式细胞术、转移和管状形成实验评估circPKM2对NSCLC恶性表型的影响。通过Western印迹法测量相关标记蛋白水平。circPKM2和MTDH在NSCLC组织和细胞中高表达，而miR-1298-5p则下调。circPKM2敲低在体外有效抑制细胞增殖、迁移、侵袭和管状形成，同时诱导细胞凋亡。circPKM2与miR-1298-5p存在潜在的靶位点，并负调节miR-1298-5p的表达。miR-1298-5p抑制剂逆转了circPKM2敲低对NSCLC进展的影响。circPKM2通过与miR-1298-5p结合来诱导MTDH的表达，从而促进NSCLC的进展。miR-1298-5p直接靶向MTDH，MTDH的添加部分减弱了miR-1298-5p对NSCLC进展的抑制作用。此外，circPKM2的下调显著减缓了体内异种移植瘤的生长。我们的研究结果表明，circPKM2通过调节miR-1298-5p/MTDH轴介导NSCLC的进展，为NSCLC提供了新的治疗靶点。© 2023 The Authors. 中国肺癌小组和John Wiley & Sons Australia, Ltd.发表的《Thoracic Cancer》

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.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.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.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.