Research Paper Volume 13, Issue 16 pp 20372—20382
Circular RNA circRHOT1 contributes to pathogenesis of non-small cell lung cancer by epigenetically enhancing C-MYC expression through recruiting KAT5
- 1 Department of Anesthesiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
Received: March 22, 2021 Accepted: May 20, 2021 Published: August 18, 2021https://doi.org/10.18632/aging.203417
How to Cite
Copyright: © 2021 Ren et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Non-small cell lung cancer (NSCLC) one of the most prevalent and severe malignancies globally and the molecular mechanisms of NSCLC are poor understood, limiting the development of diagnostic biomarkers and targeted therapies. Circular RNAs (circRNAs) have been identified as a sort of critical regulator in cancer progression. In this study, we identities the epigenetic regulation function of circular RNA circRHOT1 in promoting NSCLC cell proliferation. We found that circRHOT1 were elevated in the clinical tumor tissues relative to that in the peritumor tissues from NSCLC patients. circRHOT1 was up-regulated in human lung cancer cell lines compared with normal human lung epithelial cell line. MTT assays revealed that the silencing of circRHOT1 by siRNA suppressed cell viabilities of NSCLC cells. Colony formation and Edu assays confirmed that circRHOT1 knockdown attenuated NSCLC cell proliferation in vitro. Meanwhile, the depletion of circRHOT1 induced NSCLC cell apoptosis and cell cycle arrest in vitro. Mechanically, the depletion of circRHOT1 remarkably reduced c-MYC mRNA and protein expression in NSCLC cells. Inhibition of circRHOT1 reduced the enrichment of transcription active marker histone H3 lysine 27 acetylation (H3K27ac) and RNA polymerase II on the promoter of c-MYC. RNA pull down analysis showed that circRHOT1 was able to directly interact with acetyltransferase KAT5 in NSCLC cells. In summary, we concluded that circRHOT1 contributed to pathogenesis of NSCLC by epigenetically enhancing c-MYC expression through recruiting KAT5. CircRHOT1 and KAT5 may be used as the potential targets for NSCLC therapy.