Long non-coding RNA HOTAIR is a marker for hepatocellular carcinoma progression and tumor recurrence

被引:113
作者
Gao, Jian-zhi [1 ,2 ]
Li, Jia [2 ,3 ]
Du, Jing-li [2 ]
Li, Xiao-lei [4 ]
机构
[1] Xinxiang Med Coll, Dept Basic Med Sci, 601 Jinsui Rd, Xinxiang 453003, Henan, Peoples R China
[2] Chinese Peoples Liberat Army Gen Hosp, Dept Pathol, Beijing 100853, Peoples R China
[3] Capital Univ Med Sci, Dept Pathol, Beijing Tiantan Hosp, Beijing 100050, Peoples R China
[4] Chinese Peoples Liberat Army Gen Hosp, Inst Basic Med, Dept Mol Biol, Beijing 100853, Peoples R China
关键词
long non-coding RNA; HOX transcript antisense RNA; hepatocellular carcinoma; progression; recurrence; EPITHELIAL-MESENCHYMAL TRANSITION; SQUAMOUS-CELL CARCINOMA; THERAPEUTIC TARGETS; PROSTATE-CANCER; POOR-PROGNOSIS; METASTASIS; EXPRESSION; PATHWAY; OVEREXPRESSION; GENE;
D O I
10.3892/ol.2016.4130
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The present study aimed to investigate the expression level of HOX transcript antisense RNA (HOTAIR) in hepatocellular carcinoma (HCC) and its association with various clinicopathological characteristics, and to further explore the molecular mechanisms of HOTAIR function in HCC. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression level of HOTAIR in 60 paired fresh HCC samples and adjacent normal liver tissue samples. The association between HOTAIR expression and clinicopathological parameters was analyzed. Lentivirus-mediated HOTAIR-specific small hairpin RNA vectors were transfected into HepG2 cells. Cell proliferation and invasion in vitro were examined by MTT and Transwell assays, respectively. A xenograft model was used to analyze the tumorigenesis of liver cancer cells in vivo. In addition, semi-quantitative RT-PCR was used to detect the expression level of Wnt/-catenin signaling molecules under the condition of HOTAIR inhibition. The results revealed that the expression level of HOTAIR in HCC tissues was higher than that in adjacent non-cancerous tissues. HOTAIR expression was significantly associated with poor tumor differentiation (P=0.002), metastasis (P=0.002) and early recurrence (P=0.001). In vitro, the inhibition of HOTAIR in liver cancer cells resulted in the suppression of cell proliferation and invasion. HOTAIR depletion significantly inhibited the rate of growth of liver cancer cells in vivo. Furthermore, the expression levels of Wnt and -catenin were downregulated when HOTAIR expression was suppressed. In conclusion, HOTAIR is important in the progression and recurrence of HCC, partly through the regulation of the Wnt/-catenin signaling pathway. Targeting HOTAIR may be a novel therapeutic strategy for HCC.
引用
收藏
页码:1791 / 1798
页数:8
相关论文
共 40 条
[1]   Primary liver cancer:: Worldwide incidence and trends [J].
Bosch, FX ;
Ribes, J ;
Díaz, M ;
Cléries, R .
GASTROENTEROLOGY, 2004, 127 (05) :S5-S16
[2]   Histone macroH2A1 is concentrated in the inactive X chromosome of female mammals [J].
Costanzi, C ;
Pehrson, JR .
NATURE, 1998, 393 (6685) :599-601
[3]   The Wnt/β-catenin pathway as a therapeutic target in human hepatocellular carcinoma [J].
Dahmani, Rajae ;
Just, Pierre-Alexandre ;
Perret, Christine .
CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY, 2011, 35 (11) :709-713
[4]   The American Joint Committee on Cancer: the 7th Edition of the AJCC Cancer Staging Manual and the Future of TNM [J].
Edge, Stephen B. ;
Compton, Carolyn C. .
ANNALS OF SURGICAL ONCOLOGY, 2010, 17 (06) :1471-1474
[5]   Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis [J].
El-Serag, Hashem B. ;
Rudolph, Lenhard .
GASTROENTEROLOGY, 2007, 132 (07) :2557-2576
[6]   Hepatocellular carcinoma pathogenesis: from genes to environment [J].
Farazi, Paraskevi A. ;
DePinho, Ronald A. .
NATURE REVIEWS CANCER, 2006, 6 (09) :674-687
[7]   Regulation of apoptosis by a prostate-specific and prostate cancer-associated noncoding gene, PCGEM1 [J].
Fu, XQ ;
Ravindranath, L ;
Tran, N ;
Petrovics, G ;
Srivastava, S .
DNA AND CELL BIOLOGY, 2006, 25 (03) :135-141
[8]   HOTAIR, a prognostic factor in esophageal squamous cell carcinoma, inhibits WIF-1 expression and activates Wnt pathway [J].
Ge, Xiao-Song ;
Ma, Hua-Juan ;
Zheng, Xiao-Hui ;
Ruan, Hong-Lian ;
Liao, Xiao-Yu ;
Xue, Wen-Qiong ;
Chen, Yuan-Bin ;
Zhang, Ying ;
Jia, Wei-Hua .
CANCER SCIENCE, 2013, 104 (12) :1675-1682
[9]   Large Intervening Non-coding RNA HOTAIR is Associated with Hepatocellular Carcinoma Progression [J].
Geng, Y. J. ;
Xie, S. L. ;
Li, Q. ;
Ma, J. ;
Wang, G. Y. .
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH, 2011, 39 (06) :2119-2128
[10]   Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis [J].
Gupta, Rajnish A. ;
Shah, Nilay ;
Wang, Kevin C. ;
Kim, Jeewon ;
Horlings, Hugo M. ;
Wong, David J. ;
Tsai, Miao-Chih ;
Hung, Tiffany ;
Argani, Pedram ;
Rinn, John L. ;
Wang, Yulei ;
Brzoska, Pius ;
Kong, Benjamin ;
Li, Rui ;
West, Robert B. ;
van de Vijver, Marc J. ;
Sukumar, Saraswati ;
Chang, Howard Y. .
NATURE, 2010, 464 (7291) :1071-U148