p53-induced microRNA-1246 inhibits the cell growth of human hepatocellular carcinoma cells by targeting NFIB

被引:58
作者
Zhang, Quan [1 ,3 ]
Cao, Li-Ye [2 ]
Cheng, Shu-Jie [3 ]
Zhang, Ai-Min [3 ]
Jin, Xiao-Shi [3 ]
Li, Yong [1 ]
机构
[1] Hebei Med Univ, Affiliated Hosp 4, Dept Surg, Shijiazhuang 050011, Hebei, Peoples R China
[2] Hebei Univ, Affiliated Hosp, Dept Ultrasound, Baoding, Hebei, Peoples R China
[3] Hebei Univ, Affiliated Hosp, Dept Surg, Baoding, Hebei, Peoples R China
关键词
miR-1246; NFIB; cell proliferation; HCC; TUMOR-SUPPRESSOR; GENE-EXPRESSION; P53; NETWORK; CANCER; PROLIFERATION; MIR-1246; MIR-34A; ACTIVATION; APOPTOSIS; MIGRATION;
D O I
10.3892/or.2015.3715
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In recent years, miR-1246 has been identified as a transcriptional target of p53 in Down syndrome and may provide a new p53-miR-1246-DYRK1A-NFAT pathway in cancer. The present study aimed to explore the role of miR-1246 in the tumorigenesis of human hepatocellular carcinoma (HCC). We found that wild-type p53 regulated the expression of miR-1246 in HCC cell lines, and alteration of miR-1246 modulated cell proliferation, colony formation ability and apoptosis. The nuclear factor I/B (NFIB), an oncogene, was identified as a direct target gene of miR-1246 using a fluorescent reporter assay. Overexpression of NFIB abolished the regulation of cell apoptosis caused by miR-1246 in HepG2 cells. This finding suggests that miR-1246 is regulated by p53 and suppresses the growth of human HCC by targeting NFIB. Here, we propose a new p53-miR-1246-NFIB pathway in HCC.
引用
收藏
页码:1335 / 1341
页数:7
相关论文
共 31 条
[1]   p53-mediated activation of miRNA34 candidate tumor-suppressor genes [J].
Bommer, Guido T. ;
Gerin, Isabelle ;
Feng, Ying ;
Kaczorowski, Andrew J. ;
Kuick, Rork ;
Love, Robert E. ;
Zhai, Yali ;
Giordano, Thomas J. ;
Qin, Zhaohui S. ;
Moore, Bethany B. ;
MacDougald, Ormond A. ;
Cho, Kathleen R. ;
Fearon, Eric R. .
CURRENT BIOLOGY, 2007, 17 (15) :1298-1307
[2]   Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis [J].
Chang, Tsung-Cheng ;
Wentzel, Erik A. ;
Kent, Oliver A. ;
Ramachandran, Kalyani ;
Mullendore, Michael ;
Lee, Kwang Hyuck ;
Feldmann, Georg ;
Yamakuchi, Munekazu ;
Ferlito, Marcella ;
Lowenstein, Charles J. ;
Arking, Dan E. ;
Beer, Michael A. ;
Maitra, Anirban ;
Mendell, Joshua T. .
MOLECULAR CELL, 2007, 26 (05) :745-752
[3]   Real-time quantification of microRNAs by stem-loop RT-PCR [J].
Chen, CF ;
Ridzon, DA ;
Broomer, AJ ;
Zhou, ZH ;
Lee, DH ;
Nguyen, JT ;
Barbisin, M ;
Xu, NL ;
Mahuvakar, VR ;
Andersen, MR ;
Lao, KQ ;
Livak, KJ ;
Guegler, KJ .
NUCLEIC ACIDS RESEARCH, 2005, 33 (20) :e179.1-e179.9
[4]   MiR-1246 promotes SiHa cervical cancer cell proliferation, invasion, and migration through suppression of its target gene thrombospondin 2 [J].
Chen, Junying ;
Yao, Desheng ;
Zhao, Shan ;
He, Chanjuan ;
Ding, Nan ;
Li, Li ;
Long, Fengyi .
ARCHIVES OF GYNECOLOGY AND OBSTETRICS, 2014, 290 (04) :725-732
[5]   p53-family proteins and their regulators: hubs and spokes in tumor suppression [J].
Collavin, L. ;
Lunardi, A. ;
Del Sal, G. .
CELL DEATH AND DIFFERENTIATION, 2010, 17 (06) :901-911
[6]   MicroRNA-34b and MicroRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth [J].
Corney, David C. ;
Flesken-Nikitin, Andrea ;
Godwin, Andrew K. ;
Wang, Wei ;
Nikitin, Alexander Yu. .
CANCER RESEARCH, 2007, 67 (18) :8433-8438
[7]   Nuclear factor I/B is an oncogene in small cell lung cancer [J].
Dooley, Alison L. ;
Winslow, Monte M. ;
Chiang, Derek Y. ;
Banerji, Shantanu ;
Stransky, Nicolas ;
Dayton, Talya L. ;
Snyder, Eric L. ;
Senna, Stephanie ;
Whittaker, Charles A. ;
Bronson, Roderick T. ;
Crowley, Denise ;
Barretina, Jordi ;
Garraway, Levi ;
Meyerson, Matthew ;
Jacks, Tyler .
GENES & DEVELOPMENT, 2011, 25 (14) :1470-1475
[8]   Tumor suppressor p53 meets microRNAs [J].
Feng, Zhaohui ;
Zhang, Cen ;
Wu, Rui ;
Hu, Wenwei .
JOURNAL OF MOLECULAR CELL BIOLOGY, 2011, 3 (01) :44-50
[9]   Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008 [J].
Ferlay, Jacques ;
Shin, Hai-Rim ;
Bray, Freddie ;
Forman, David ;
Mathers, Colin ;
Parkin, Donald Maxwell .
INTERNATIONAL JOURNAL OF CANCER, 2010, 127 (12) :2893-2917
[10]   microRNAs join the p53 network - another piece in the tumour-suppression puzzle [J].
He, Lin ;
He, Xingyue ;
Lowe, Scott W. ;
Hannon, Gregory J. .
NATURE REVIEWS CANCER, 2007, 7 (11) :819-822