LncRNA HClnc1 facilitates hepatocellular carcinoma progression by regulating PKM2 signaling and indicates poor survival outcome after hepatectomy

被引:8
作者
Zhu, Qian [1 ,2 ]
Lei, Zhengqing [1 ]
Xu, Chang [3 ]
Zhang, Zheng [1 ]
Yu, Zeqian [1 ]
Cheng, Zhangjun [1 ]
Xiao, Pengfeng [4 ]
Li, Shufeng [5 ]
Yu, Weiping [6 ]
Zhou, Jiahua [1 ,7 ]
机构
[1] Southeast Univ, Zhongda Hosp, Sch Med, Dept Hepatobiliary Surg, Nanjing, Jiangsu, Peoples R China
[2] Wuhan Univ, Zhongnan Hosp, Dept Hepatobiliary & Pancreat Surg, Wuhan, Hubei, Peoples R China
[3] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Biliary Surg 1, Shanghai, Peoples R China
[4] Southeast Univ, Natl Demonstrat Ctr Expt Biomed Engn Educ, Sch Biol Sci & Med Engn, State Key Lab Bioelect, Nanjing, Jiangsu, Peoples R China
[5] Southeast Univ, Med Sch, Dept Biochem & Mol Biol, Nanjing, Jiangsu, Peoples R China
[6] Southeast Univ, Sch Med, Dept pathophysiol, Nanjing, Jiangsu, Peoples R China
[7] Southeast Univ, Zhongda Hosp, Sch Med, Dept Hepatobiliary Surg, 87 Dingjiaqiao, Nanjing 210009, Jiangsu, Peoples R China
来源
CANCER MEDICINE | 2023年 / 12卷 / 13期
基金
中国国家自然科学基金;
关键词
HClnc1; hepatocellular carcinoma; long noncoding RNA; PKM2; prognosis; Warburg effect; LONG NONCODING RNA; CELL-PROLIFERATION; IN-VIVO; PROMOTES; CANCER; TARGET; IDENTIFICATION; ASSOCIATION; EXPRESSION; GENE;
D O I
10.1002/cam4.6117
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
AimLong noncoding RNAs (lncRNAs) are key mediators with a wide range of pathophysiological functions, but their role in human hepatocellular carcinoma (HCC) is still unclear.MethodsAn unbiased microarray study evaluated a novel lncRNA, HClnc1, that is linked to the development of HCC. In vitro cell proliferation assays and an in vivo xenotransplanted HCC tumor model were performed to determine its functions, followed by antisense oligo-coupled mass spectrometry to identify HClnc1-interacting proteins. To study relevant signaling pathways, in vitro experiments were performed, including chromatin isolation by RNA purification, RNA immunoprecipitation, luciferase, and RNA pull-down assay.ResultsHClnc1 levels were considerably greater in patients with advanced tumor-node-metastatic stages, and it was found to be inversely connected to survival rates. Moreover, the proliferative and invasive potential of the HCC cells was attenuated by HClnc1 RNA knockdown in vitro, while HCC tumor growth and metastasis were found to be reduced in vivo. HClnc1 interacted with pyruvate kinase M2 (PKM2) to prevent its degradation and thus facilitated aerobic glycolysis and PKM2-STAT3 signaling.ConclusionsHClnc1 is involved in a novel epigenetic mechanism of HCC tumorigenesis and PKM2 regulation. HClnc1 is not only a more accurate prognostic indicator of HCC but also a potential therapeutic target for HCC treatment.
引用
收藏
页码:14526 / 14544
页数:19
相关论文
共 34 条
[1]   PKM2 promotes tumor angiogenesis by regulating HIF-1α through NF-κB activation [J].
Azoitei, Ninel ;
Becher, Alexander ;
Steinestel, Konrad ;
Rouhi, Arefeh ;
Diepold, Kristina ;
Genze, Felicitas ;
Simmet, Thomas ;
Seufferlein, Thomas .
MOLECULAR CANCER, 2016, 15
[2]   The Long Intergenic Noncoding RNA UFC1, a Target of MicroRNA 34a, Interacts With the mRNA Stabilizing Protein HuR to Increase Levels of β-Catenin in HCC Cells [J].
Cao, Chuanhui ;
Sun, Jingyuan ;
Zhang, Dongyan ;
Guo, Xuejun ;
Xie, Liwei ;
Li, Xin ;
Wu, Dehua ;
Liu, Li .
GASTROENTEROLOGY, 2015, 148 (02) :415-U249
[3]   Quantitative image analysis in the assessment of diffuse large B-cell lymphoma [J].
Chabot-Richards, Devon S. ;
Martin, David R. ;
Myers, Orrin B. ;
Czuchlewski, David R. ;
Hunt, Kristin E. .
MODERN PATHOLOGY, 2011, 24 (12) :1598-1605
[4]   Small GTPase RBJ Mediates Nuclear Entrapment of MEK1/MEK2 in Tumor Progression [J].
Chen, Taoyong ;
Yang, Mingjin ;
Yu, Zhou ;
Tang, Songqing ;
Wang, Chen ;
Zhu, Xuhui ;
Guo, Jun ;
Li, Nan ;
Zhang, Weiping ;
Hou, Jin ;
Liu, Haibo ;
Han, Chaofeng ;
Liu, Qiuyan ;
Gu, Yan ;
Qian, Cheng ;
Wan, Tao ;
Cui, Long ;
Zhu, Minghua ;
Zheng, Weiqiang ;
Cao, Xuetao .
CANCER CELL, 2014, 25 (05) :682-696
[5]   Cancer Statistics in China, 2015 [J].
Chen, Wanqing ;
Zheng, Rongshou ;
Baade, Peter D. ;
Zhang, Siwei ;
Zeng, Hongmei ;
Bray, Freddie ;
Jemal, Ahmedin ;
Yu, Xue Qin ;
He, Jie .
CA-A CANCER JOURNAL FOR CLINICIANS, 2016, 66 (02) :115-132
[6]  
Chu C., 2012, JOVE-J VIS EXP, V25
[7]   Germline loss of PKM2 promotes metabolic distress and hepatocellular carcinoma [J].
Dayton, Talya L. ;
Gocheva, Vasilena ;
Miller, Kathryn M. ;
Israelsen, William J. ;
Bhutkar, Arjun ;
Clish, Clary B. ;
Davidson, Shawn M. ;
Luengo, Alba ;
Bronson, Roderick T. ;
Jacks, Tyler ;
Vander Heiden, Matthew G. .
GENES & DEVELOPMENT, 2016, 30 (09) :1020-1033
[8]   Association of long noncoding RNA and c-JUN expression in hepatocellular carcinoma [J].
El-Tawdi, Ahmed H. F. ;
Matboli, Marwa ;
El-Nakeep, Sarah ;
Azazy, Ahmed E. M. ;
Abdel-Rahman, Omar .
EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY, 2016, 10 (07) :869-877
[9]   Hallmarks of Cancer: The Next Generation [J].
Hanahan, Douglas ;
Weinberg, Robert A. .
CELL, 2011, 144 (05) :646-674
[10]   Identification of miRNomes in Human Liver and Hepatocellular Carcinoma Reveals miR-199a/b-3p as Therapeutic Target for Hepatocellular Carcinoma [J].
Hou, Jin ;
Lin, Li ;
Zhou, Weiping ;
Wang, Zhengxin ;
Ding, Guoshan ;
Dong, Qiongzhu ;
Qin, Lunxiu ;
Wu, Xiaobing ;
Zheng, Yuanyuan ;
Yang, Yun ;
Tian, Wei ;
Zhang, Qian ;
Wang, Chunmei ;
Zhang, Qinghua ;
Zhuang, Shi-Mei ;
Zheng, Limin ;
Liang, Anmin ;
Tao, Wenzhao ;
Cao, Xuetao .
CANCER CELL, 2011, 19 (02) :232-243