Abstract
circNOL10 is a circular RNA expressed at low levels in lung cancer, though its functions in lung cancer remain unknown. Here, the function and molecular mechanism of circNOL10 in lung cancer development are investigated using in vitro and in vivo studies, and it is shown that circNOL10 significantly inhibits the development of lung cancer and that circNOL10 expression is co-regulated by methylation of its parental gene Pre-NOL10 and by splicing factor epithelial splicing regulatory protein 1 (ESRP1). circNOL10 promotes the expression of transcription factor sex comb on midleg-like 1 (SCML1) by inhibiting transcription factor ubiquitination and thus also affects regulation of the humanin (HN) polypeptide family by SCML1. circNOL10 also affects mitochondrial function through regulating the humanin polypeptide family and affecting multiple signaling pathways, ultimately inhibiting cell proliferation and cell cycle progression, and promoting the apoptosis of lung cancer cells, thereby inhibiting lung cancer development. This study investigates the functions and molecular mechanisms of circNOL10 in the development of lung cancer and reveals its involvement in the transcriptional regulation of the HN polypeptide family by SCML1. The results also demonstrate the inhibitory effect of HN on lung cancer cells growth. These findings may identify novel targets for the molecular therapy of lung cancer.
| Original language | English |
|---|---|
| Article number | 1800654 |
| Journal | Advanced Science |
| Volume | 6 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jan 23 2019 |
Bibliographical note
Publisher Copyright:© 2018 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Funding
A.N. and L.C. contributed equally to this work. Y.J., A.N., C.Y., S.L., and Z.W. designed the research. A.N., L.C, N.Z., Y.Y.J., X.L., H.Z., and Y.L. performed the experiments. A.N. and Y.J. wrote the manuscript. All authors analyzed the data and revised the manuscript. Y.J. was responsible for research supervision and funding acquisition. The authors would like to thank Professor Wen Chen, Professor Shimei Zhuang, Professor Fei Zou, and Xingguo Liu for valuable suggestions. The authors also thank Lijun Dai for providing assistance with the animal experiments, and Qiaoyuan Yang, Jiabin Dai, and Shaozhu Zhang for help with collecting human tissue samples. This study was supported by the National Natural Science Foundation of China (Grant Nos. 91643204, 81573180, and 81872652 to Y.J.), the Science and Technology Program of Guangzhou (Grant No. 201707020043 to Y.J.), the University Chief Scientist Program of Guangzhou (Grant No. 1201541575 to Y.J.), and the Guangdong Natural Science Foundation (Grant No. 2018B030311019 to Y.J.).
| Funders | Funder number |
|---|---|
| University Chief Scientist Program of Guangzhou | 1201541575 |
| National Natural Science Foundation of China (NSFC) | 81573180, 91643204, 81872652 |
| Natural Science Foundation of Guangdong Province | 2018B030311019 |
| Guangzhou Science and Technology Program key projects | 201707020043 |
| Program of Shanghai Subject Chief Scientist |
Keywords
- circular RNA
- humanin polypeptide
- lung cancer
- transcriptional regulation
ASJC Scopus subject areas
- Medicine (miscellaneous)
- General Chemical Engineering
- General Materials Science
- Biochemistry, Genetics and Molecular Biology (miscellaneous)
- General Engineering
- General Physics and Astronomy
