miR-106b-5p promotes aggressive progression of hepatocellular carcinoma via targeting RUNX3

被引:48
作者
Gu, Hao [1 ]
Gu, Shensen [1 ]
Zhang, Xinlong [1 ]
Zhang, Songjiang [1 ]
Zhang, Dongming [1 ]
Lin, Junsheng [1 ]
Hasengbayi, Saiken [1 ]
Han, Wei [1 ]
机构
[1] Xinjiang Med Univ, Digest Vasc Surg Ctr, Xinjiang 830054, Peoples R China
关键词
cell viability; hepatocellular carcinoma; invasion; microRNA-106b-5p; overall survival; recurrence-free survival; MICRORNA-106B-5P; MICRORNAS; CISPLATIN; EXPRESSION; RESISTANCE; PROGNOSIS; CANCER; CELLS; RNA;
D O I
10.1002/cam4.2511
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background and Objectives The roles of microRNA(miR)-106b-5p in hepatocellular carcinoma (HCC) remain unclear. We aimed here to investigate the clinical significance of miR-106b-5p expression in HCC and its underlying mechanisms. Methods Expression levels of miR-106b-5p in 108 HCC clinical samples by quantitative real-time reverse transcription PCR. Associations of miR-106b-5p expression with various clinicopathological features and patients' prognosis were evaluated by Chi-square test, Kaplan-Meier, and Cox proportional regression analyses, respectively. The target gene of miR-106b-5p and their functions in HCC cells were investigated by luciferase reporter, CCK-8, and Transwell Matrigel invasion assays. Results miR-106b-5p expression was markedly higher in HCC tissues than in noncancerous adjacent liver tissues (P < .001). miR-106b-5p upregulation was significantly associated with advanced TNM stage (P = .02), short recurrence-free (P = .005), and overall (P = .001) survivals. Importantly, miR-106b-5p expression was an independent predictor of poor prognosis (P < .05). RUNX3 was identified as a direct target gene of miR-106b-5p in HCC cells. Functionally, miR-106b-5p upregulation promoted the viability and invasion of HCC cells, while enforced RUNX3 expression reversed the oncogenic effects of miR-106b-5p overexpression. Conclusions miR-106b-5p may serve as a potent prognostic marker for tumor recurrence and survival of HCC patients. miR-106b-5p may exert an oncogenic role in HCC via regulating its target gene RUNX3.
引用
收藏
页码:6756 / 6767
页数:12
相关论文
共 30 条
[1]   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
[2]   Loss of expression rather than cytoplasmic mislocalization of RUNX3 predicts worse outcome in non-small cell lung cancer [J].
Chen, Xiaohui ;
Deng, Yujie ;
Shi, Yi ;
Zhu, Weifeng ;
Cai, Yibin ;
Xu, Chunwei ;
Zhu, Kunshou ;
Zheng, Xiongwei ;
Chen, Gang ;
Xie, Qi ;
Weng, Guoxing .
ONCOLOGY LETTERS, 2018, 15 (04) :5043-5055
[3]   BRD4 regulates cellular senescence in gastric cancer cells via E2F/miR-106b/p21 axis [J].
Dong, Xingchen ;
Hu, Xiangming ;
Chen, Jinjing ;
Hu, Dan ;
Chen, Lin-Feng .
CELL DEATH & DISEASE, 2018, 9
[4]   Oncomirs - microRNAs with a role in cancer [J].
Esquela-Kerscher, A ;
Slack, FJ .
NATURE REVIEWS CANCER, 2006, 6 (04) :259-269
[5]   Hepatocellular carcinoma [J].
Forner, Alejandro ;
Llovet, Josep M. ;
Bruix, Jordi .
LANCET, 2012, 379 (9822) :1245-1255
[6]   RUNX3 regulates hepatocellular carcinoma cell metastasis via targeting miR-186/E-cadherin/EMT pathway [J].
Gou, Yuli ;
Zhai, Fangbing ;
Zhang, Liang ;
Cui, Lan .
ONCOTARGET, 2017, 8 (37) :61475-61486
[7]   Upregulation of microRNA-372 associates with tumor progression and prognosis in hepatocellular carcinoma [J].
Gu, Hao ;
Guo, Xiaodong ;
Zou, Lin ;
Zhu, Haiyan ;
Zhang, Jinhui .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 2013, 375 (1-2) :23-30
[8]   A microRNA polycistron as a potential human oncogene [J].
He, L ;
Thomson, JM ;
Hemann, MT ;
Hernando-Monge, E ;
Mu, D ;
Goodson, S ;
Powers, S ;
Cordon-Cardo, C ;
Lowe, SW ;
Hannon, GJ ;
Hammond, SM .
NATURE, 2005, 435 (7043) :828-833
[9]  
He L., 2004, NAT REV GENET, V5, P522
[10]   MicroRNAs and gene regulatory networks: managing the impact of noise in biological systems [J].
Herranz, Hector ;
Cohen, Stephen M. .
GENES & DEVELOPMENT, 2010, 24 (13) :1339-1344