MicroRNA-125b Functions as a Tumor Suppressor in Hepatocellular Carcinoma Cells

被引:77
作者
Jia, Hong-Yan [1 ]
Wang, Yu-Xuan [2 ]
Yan, Wen-Ting [3 ,4 ]
Li, Hui-Yu [1 ]
Tian, Yan-Zhang [1 ]
Wang, Shi-Ming [1 ]
Zhao, Hao-Liang [1 ]
机构
[1] Shanxi Med Univ, Hosp 1, Dept Surg, Taiyuan 030001, Peoples R China
[2] Shanxi Canc Hosp, Dept Thorac Surg, Taiyuan 030001, Peoples R China
[3] Chinese Acad Med Sci, Inst Basic Med Sci, Dept Biochem, Beijing 100005, Peoples R China
[4] Peking Union Med Coll, Natl Lab Med Mol Biol, Beijing 100005, Peoples R China
关键词
hepatocellular carcinoma; miR-125b; Mcl-1; IL6R; EXPRESSION; PROLIFERATION; INTERLEUKIN-6; MIR-125B; BIOGENESIS; SURVIVAL; PATHWAY; GROWTH; MCL-1;
D O I
10.3390/ijms13078762
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
MicroRNAs (miRNAs) are important regulators of multiple cellular processes, and the deregulation of miRNA is a common event in diverse human diseases, particularly cancer. However, the mechanisms underlying the relationship between disordered miRNA expression and tumorigenesis have remained largely unknown. In this study, we demonstrated the down-regulation of miR-125b in hepatocellular carcinoma (HCC) tissues and HCC cell lines by Northern blot and quantitative RT-PCR analyses. The ectopic expression of miR-125b reduced the cellular proliferation and cell cycle progression of HCC cells by targeting Mcl-1 and IL6R. Furthermore, the miR-125b-induced inhibition of cell proliferation was rescued by the expression of Mcl-1 or IL6R variants that lacked 3' UTRs. Thus, this study revealed the differential expression of miR-125b in HCC cells and elucidated its potential as a tumor suppressor in HCC development.
引用
收藏
页码:8762 / 8774
页数:13
相关论文
共 34 条
[1]   Epigenetic Silencing of the Tumor Suppressor MicroRNA Hsa-miR-124a Regulates CDK6 Expression and Confers a Poor Prognosis in Acute Lymphoblastic Leukemia [J].
Agirre, Xabier ;
Vilas-Zornoza, Amaia ;
Jimenez-Velasco, Antonio ;
Ignacio Martin-Subero, Jose ;
Cordeu, Lucia ;
Garate, Leire ;
San Jose-Eneriz, Edurne ;
Abizanda, Gloria ;
Rodriguez-Otero, Paula ;
Fortes, Puri ;
Rifon, Jose ;
Bandres, Eva ;
Jose Calasanz, Maria ;
Martin, Vanesa ;
Heiniger, Anabel ;
Torres, Antonio ;
Siebert, Reiner ;
Roman-Gomez, Jose ;
Prosper, Felipe .
CANCER RESEARCH, 2009, 69 (10) :4443-4453
[2]   Mcl-1 is a potential therapeutic target in multiple types of cancer [J].
Akgul, C. .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2009, 66 (08) :1326-1336
[3]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[4]   Molecular Profiling Uncovers a p53-Associated Role for MicroRNA-31 in Inhibiting the Proliferation of Serous Ovarian Carcinomas and Other Cancers [J].
Creighton, Chad J. ;
Fountain, Michael D. ;
Yu, Zhifeng ;
Nagaraja, Ankur K. ;
Zhu, Huifeng ;
Khan, Mahjabeen ;
Olokpa, Emuejevoke ;
Zariff, Azam ;
Gunaratne, Preethi H. ;
Matzuk, Martin M. ;
Anderson, Matthew L. .
CANCER RESEARCH, 2010, 70 (05) :1906-1915
[5]   ER Stress Negatively Modulates the Expression of the miR-199a/214 Cluster to Regulates Tumor Survival and Progression in Human Hepatocellular Cancer [J].
Duan, Quanlu ;
Wang, Xingxu ;
Gong, Wei ;
Ni, Li ;
Chen, Chen ;
He, Xingxing ;
Chen, Fuqiong ;
Yang, Lei ;
Wang, Peihua ;
Wang, Dao Wen .
PLOS ONE, 2012, 7 (02)
[6]   Diagnosis and treatment of hepatocellular carcinoma [J].
El-Serag, Hashem B. ;
Marrero, Jorge A. ;
Rudolph, Lenhard ;
Reddy, K. Rajender .
GASTROENTEROLOGY, 2008, 134 (06) :1752-1763
[7]   Dysregulation of apoptosis in hepatocellular carcinoma cells [J].
Fabregat, Isabel .
WORLD JOURNAL OF GASTROENTEROLOGY, 2009, 15 (05) :513-520
[8]   The promyelocytic leukemia zinc finger-microRNA-221/-222 pathway controls melanoma progression through multiple oncogenic mechanisms [J].
Felicetti, Federica ;
Errico, M. Cristina ;
Bottero, Lisabianca ;
Segnalini, Patrizia ;
Stoppacciaro, Antonella ;
Biffoni, Mauro ;
Felli, Nadia ;
Mattia, Gianfranco ;
Petrini, Marina ;
Colombo, Mario P. ;
Peschle, Cesare ;
Care, Alessandra .
CANCER RESEARCH, 2008, 68 (08) :2745-2754
[9]  
Fleischer B, 2006, INT J ONCOL, V28, P25
[10]   Downregulation of miR-125b in metastatic cutaneous malignant melanoma [J].
Glud, Martin ;
Rossing, Maria ;
Hother, Christoffer ;
Holst, Line ;
Hastrup, Nina ;
Nielsen, Finn C. ;
Gniadecki, Robert ;
Drzewiecki, Krzysztof T. .
MELANOMA RESEARCH, 2010, 20 (06) :479-484