Circular RNA circNOL10 Inhibits Lung Cancer Development by Promoting SCLM1-Mediated Transcriptional Regulation of the Humanin Polypeptide Family

被引:87
作者
Nan, Aruo [1 ]
Chen, Lijian [1 ]
Zhang, Nan [1 ]
Jia, Yangyang [1 ]
Li, Xin [1 ]
Zhou, Hanyu [1 ]
Ling, Yihui [1 ]
Wang, Zhishan [2 ]
Yang, Chengfeng [2 ]
Liu, Shin [3 ]
Jiang, Yiguo [1 ]
机构
[1] Guangzhou Med Univ, State Key Lab Resp Dis, Inst Chem Carcinogenesis, Guangzhou 511436, Guangdong, Peoples R China
[2] Univ Kentucky, Dept Toxicol & Canc Biol, Ctr Res Environm Dis, Coll Med, Lexington, KY 40536 USA
[3] Chinese Acad Sci, State Key Lab Environm Chem & Ecotoxicol, Res Ctr Ecoenvironm Sci, Beijing 100085, Peoples R China
基金
中国国家自然科学基金;
关键词
circular RNA; humanin polypeptide; lung cancer; transcriptional regulation; MALIGNANT-TRANSFORMATION; TRANSLATION; EXPRESSION; APOPTOSIS;
D O I
10.1002/advs.201800654
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
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页数:16
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