Circular RNA Eps15-homology domain containing protein 2 motivates proliferation, glycolysis but refrains autophagy in non-small cell lung cancer via crosstalk with microRNA-3186-3p and forkhead box K1

• Published in: Bioengineered Vol. 13; no. 3; pp. 6464 - 6475
• Main Authors: Zhang, Fan, Zhang, Tieying, Zhao, ZiRan, Ji, Ying, Peng, Yue, Zhao, Liang
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.03.2022
• Subjects: Animals; autophagy; Autophagy - genetics; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell Proliferation - genetics; circular RNA Eps15-homology domain containing protein 2; Forkhead Transcription Factors - genetics; glycolysis; Glycolysis - genetics; Humans; Lung - pathology; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Mice; Mice, Nude; MicroRNAs - genetics; Non-small cell lung cancer; Research Paper; RNA, Circular - genetics; autophagy; circular RNA Eps15-homology domain containing protein 2; Non-small cell lung cancer; glycolysis
• ISSN: 2165-5979; 2165-5987
• DOI: 10.1080/21655979.2022.2031385

Numerous studies have clarified the involvement of circular RNAs (circRNAs) in modulating malignant behavior of non-small cell lung cancer (NSCLC), while the concrete mechanism is not completely elucidated. The aim of the study was to figure out the latent functions and molecular mechanisms of circRNA Eps15-homology domain containing protein 2 (EHD2) on NSCLC proliferation, glycolysis and autophagy. The results clarified in NSCLC elevated expression of circEHD2 and declined expression of microRNA (miR)-3186-3p. Repressive circEHD2 or enhancive miR-3186-3p facilitated cell apoptosis rate and autophagy substrates LC3BII and Beclin-1, but curbed the colony-formation and DNA replication ability of NSCLC, glucose consumption, lactic acid production, glycolytic rate-limiting enzyme HK-2 and glutamine hydrolase GLS1 and P62, while overexpressed circEHD2 was adverse. Meanwhile, the impacts of repressive and elevated circEHD2 on NSCLC were turned around via reduced miR-3186-3p or forkhead box k1 (FOXK1) separately. Mechanically, FOXK1 was augmented via circEHD2ʹs competitive integration of miR-3186-3p. Depressive circEHD2 refrained NSCLC tumor growth, which was accelerated via enhancive one. All in all, circEHD2 accelerates the proliferation and glycolysis of NSCLC, but refrains autophagy and apoptosis via strengthening FOXK1 via the adsorption of miR-3186-3p, which is supposed to be a latent molecular target for NSCLC therapy later.