LncRNA NBR2 inhibits tumorigenesis by regulating autophagy in hepatocellular carcinoma

被引:69
作者
Sheng, Jia-Qi [1 ]
Wang, Mu-Ru [1 ]
Fang, Dan [1 ]
Liu, Lian [1 ]
Huang, Wen-Jie [2 ,3 ]
Tian, De-An [1 ]
He, Xing-Xing [1 ]
Li, Pei-Yuan [1 ]
机构
[1] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Div Gastroenterol, Wuhan, Peoples R China
[2] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Hepat Surg Ctr, Wuhan, Peoples R China
[3] Clin Med Res Ctr Hepat Surg Hubei Prov, Wuhan, Peoples R China
基金
中国国家自然科学基金;
关键词
Long noncoding RNA; NBR2; Autophagy; Tumorigenesis; Hepatocellular carcinoma; LONG NONCODING RNAS; TUMOR-SUPPRESSOR; CONTRIBUTES; MECHANISMS; APOPTOSIS; DISEASE; BCL-2;
D O I
10.1016/j.biopha.2020.111023
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Long noncoding RNAs (lncRNAs) have been identified to play increasingly important roles in tumorigenesis, and they may serve as novel biomarkers for cancer therapy. LncRNA NBR2 (neighbor of BRCA1 gene 2), a novel identified lncRNA, is demonstrated to decrease in several cancers. However, it is still unknown whether lncRNA NBR2 is involved in hepatocellular carcinoma and autophagy. We found that HCC cases with lower NBR2 expression had significantly worse overall survival than those with higher NBR2 expression in advanced patients. And the expression of NBR2 was negatively correlated with the degree of malignancy of HCC cell lines and differentiation of hepatocellular carcinoma. Besides, NBR2 inhibited the proliferation, invasion, and migration of liver cancer cells. We further found that NBR2 repressed cytoprotective autophagy to restrain HCC cell proliferation. Moreover, NBR2 inhibited Beclin 1-dependent autophagy through ERK and JNK pathways. Taken together, NBR2 suppressed autophagy-induced cell proliferation at least partly through ERK and JNK pathways. These data indicated that NBR2 served as a tumor suppressor gene in hepatocellular carcinoma. The current study provides a novel insight and treatment strategy for hepatocellular carcinoma.
引用
收藏
页数:11
相关论文
共 34 条
[1]   The JNK inhibitor SP600129 enhances apoptosis of HCC cells induced by the tumor suppressor WWOX [J].
Aderca, Ileana ;
Moser, Catherine D. ;
Veerasamy, Manivannan ;
Bani-Hani, Ahmad H. ;
Bonilla-Guerrero, Ruben ;
Ahmed, Kadra ;
Shire, Abdirashid ;
Cazanave, Sophie C. ;
Montoya, Damian P. ;
Mettler, Teresa A. ;
Burgart, Lawrence J. ;
Nagorney, David M. ;
Thibodeau, Stephen N. ;
Cunningham, Julie M. ;
Lai, Jin-Ping ;
Roberts, Lewis R. .
JOURNAL OF HEPATOLOGY, 2008, 49 (03) :373-383
[2]   Specific binding of the methyl binding domain protein 2 at the BRCA1-NBR2 locus [J].
Auriol, E ;
Billard, LM ;
Magdinier, F ;
Dante, R .
NUCLEIC ACIDS RESEARCH, 2005, 33 (13) :4243-4254
[3]   NON-CODING RNAs IN DEVELOPMENT AND DISEASE: BACKGROUND, MECHANISMS, AND THERAPEUTIC APPROACHES [J].
Beermann, Julia ;
Piccoli, Maria-Teresa ;
Viereck, Janika ;
Thum, Thomas .
PHYSIOLOGICAL REVIEWS, 2016, 96 (04) :1297-1325
[4]   LncRNA NBR2 inhibits epithelial-mesenchymal transition by regulating Notch1 signaling in osteosarcoma cells [J].
Cai, Weiliang ;
Wu, Bowen ;
Li, Zhizhong ;
He, Peiheng ;
Wang, Biao ;
Cai, Anlie ;
Zhang, Xiping .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2019, 120 (02) :2015-2027
[5]   Modulating autophagy for therapeutic benefit [J].
Carew, Jennifer S. ;
Nawrocki, Steffan T. ;
Cleveland, John L. .
AUTOPHAGY, 2007, 3 (05) :464-467
[6]   The Noncoding RNA Revolution-Trashing Old Rules to Forge New Ones [J].
Cech, Thomas R. ;
Steitz, Joan A. .
CELL, 2014, 157 (01) :77-94
[7]  
Chen JX, 2015, J HEPATOL, V62, P1287, DOI 10.1016/j.jhep.2015.01.014
[8]   Beclin 1-independent pathway of damage-induced mitophagy and autophagic stress [J].
Chu, Charleen T. ;
Zhu, Jianhui ;
Dagda, Ruben .
AUTOPHAGY, 2007, 3 (06) :663-666
[9]   BMP4 promotes hepatocellular carcinoma proliferation by autophagy activation through JNK1-mediated Bcl-2 phosphorylation [J].
Deng, Ganlu ;
Zeng, Shan ;
Qu, Yanling ;
Luo, Qingqing ;
Guo, Cao ;
Yin, Ling ;
Han, Ying ;
Li, Yiyi ;
Cai, Changjing ;
Fu, Yaojie ;
Shen, Hong .
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2018, 37
[10]  
Doria A, 2013, NEW ENGL J MED, V368, P1845, DOI [10.1056/NEJMra1205406, 10.1056/NEJMc1303158]