Roles of MYC-targeting long non-coding RNA MINCR in cell cycle regulation and apoptosis in non-small cell lung Cancer

被引:40
作者
Chen, Shengjie [1 ]
Gu, Tianyi [1 ,2 ]
Lu, Ziwen [3 ]
Qiu, Lipeng [4 ]
Xiao, Guoliang [1 ,2 ]
Zhu, Xiaozhong [1 ]
Li, Feng [1 ]
Yu, Hui [1 ]
Li, Gang [1 ]
Liu, Hanqing [3 ]
机构
[1] Jiangsu Univ, Affiliated Hosp, Dept Cardiothorac Surg, Zhenjiang 212001, Jiangsu, Peoples R China
[2] Jiangsu Univ, Sch Med, Zhenjiang 212013, Jiangsu, Peoples R China
[3] Jiangsu Univ, Sch Pharm, Zhenjiang 212013, Jiangsu, Peoples R China
[4] Jiangsu Univ, Inst Life Sci, Zhenjiang 212013, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Long non-coding RNA; MINCR; Non-small cell lung cancer; C-Myc; ONCOGENIC RAS; C-MYC; PROLIFERATION; EXPRESSION; PROMOTES; PROGRESSION; SENESCENCE; INVASION; NETWORK; BRCA1;
D O I
10.1186/s12931-019-1174-z
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Background Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer death in the world, and has a relatively low survival rate. Long non-coding RNAs (lncRNAs) have been demonstrated to modulate cancer progression through a variety of molecular mechanisms. We sought to investigate the role and potential mechanism of MYC-induced long non-coding RNA (MINCR) in NSCLC. Methods Expression levels of MINCR was first identified using The Cancer Genome Atlas (TCGA), further confirmed with specimens from 29 NSCLC patients and three cell lines using qRT-PCR. Overexpression and knockdown of MINCR were performed in NSCLC cell lines through MINCR overexpression vectors and synthesized siRNAs, respectively. The roles of MINCR in NSCLC cell lines, such as cell proliferation, cell cycle arrest, and apoptosis, were identified by MTT, flow cytometry, and Western blot. The modulation of MINCR-regulated genes, including c-Myc and its downstream effectors, as well as apoptosis-associated genes, was analyzed using Western blot. Results MINCR expression was increased in NSCLC patients from TCGA datasets, and was also significantly increased in our collected specimens from NSCLC patients and NSCLC cell lines. Knocking down of MINCR greatly inhibited the growth of NSCLC cell lines PC9 and A549. In addition, silencing of MINCR induced cell cycle arrest and apoptosis. Furthermore, silencing of MINCR reduced the expression levels of oncogene c-Myc and its downstream cyclin A, cyclin D, CD4, and CDK2, as well as apoptosis-associated Bcl-2, while significantly increased the expression levels of cleaved PARP-1. In the meantime, overexpression of MINCR remarkably enhanced cell proliferation of PC9 cells and activated c-Myc and its downstream effectors. Conclusion MINCR exerted inhibitory effects on the cell cycle arrest and apoptosis of NSCLC cells by activating c-Myc and its downstream effectors, suggesting that this lncRNA could be used as a potential therapeutic target for the treatment of NSCLC.
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页数:11
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