Oncotarget

Research Papers:

LncRNA HULC enhances epithelial-mesenchymal transition to promote tumorigenesis and metastasis of hepatocellular carcinoma via the miR-200a-3p/ZEB1 signaling pathway

Shi-Peng Li, Hai-Xu Xu, Yao Yu, Jin-Dan He, Zhen Wang, Yan-Jie Xu, Chang-Ying Wang, Hai-Ming Zhang, Rong-Xin Zhang, Jian-Jun Zhang _, Zhi Yao and Zhong-Yang Shen

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Oncotarget. 2016; 7:42431-42446. https://doi.org/10.18632/oncotarget.9883

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Abstract

Shi-Peng Li1,*, Hai-Xu Xu3,*, Yao Yu1,*, Jin-Dan He1,*, Zhen Wang1, Yan-Jie Xu1, Chang-Ying Wang3, Hai-Ming Zhang1,2, Rong-Xin Zhang4, Jian-Jun Zhang1,2, Zhi Yao3, Zhong-Yang Shen1,2

1First Central Clinical College, Tianjin Medical University, Tianjin, P.R. China

2Oriental Organ Transplant Center of Tianjin First Central Hospital, Key Laboratory of Organ Transplantation of Tianjin, Tianjin, P.R.China

3Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immuno Microenvironment and Disease of the Educational Ministry, Tianjin Medical University, Tianjin, P.R.China

4Laboratory of Immunology and Inflammation, Department of Immunology, Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Basic Medical College, Tianjin Medical University, Tianjin, P.R.China

*These authors have contributed equally to this work

Correspondence to:

Jian-Jun Zhang, email: zhangjianjun9999@yeah.net

Zhong-Yang Shen, email: zhongyangshen@vip.sina.com

Rong-Xin Zhang, email: rongxinz@yahoo.com

Zhi Yao, email: yaozhi@tijmu.edu.cn

Keywords: hepatocellular carcinoma, lncRNA HULC, epithelial-mesenchymal transition, miR-200a-3p, ZEB1

Received: November 29, 2015     Accepted: May 14, 2016     Published: June 7, 2016

ABSTRACT

Highly upregulated in liver cancer (HULC), a lncRNA that is considered a key molecule in human liver cancer, has recently been revealed to be involved in hepatocellular carcinoma (HCC) development and progression [1, 2]. It has been reported that HULC can promote tumor invasion and metastasis of HCC, but its function and mechanism of action in HCC have not been elucidated. In this study, we found that HULC was aberrantly up-regulated in HCC tissues and associated with TNM stage, intrahepatic metastases, HCC recurrence, and postoperative survival. HULC depletion inhibited the growth and metastasis of HCC cell lines in vitro and in vivo. Moreover, HULC contributes to ZEB1-induced epithelial-mesenchymal transition (EMT), a requirement for tumor invasion and metastasis that plays a key role in cancer progression. This effect of ZEB1 was inhibited by HULC siRNA. We conclude that the HULC functioned as a competing endogenous RNA (ceRNA) to mediate EMT via up-regulating ZEB1. In this way, it sequesters the miR-200a-3p signaling pathway to facilitate HCC metastasis. HULC comes into play as an oncogene in HCC, acting mechanistically by inducing HCC cells to activate EMT. Such an effect promotes tumor progression and metastasis through the miR-200a-3p/ZEB1 signaling pathway. The identification of this novel pathway that links high expression levels of HULC with EMT in HCC cells may serve as the foundation for the development of novel anti-tumor therapeutics.


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