LncRNA HULC enhances epithelial-mesenchymal transition to promote tumorigenesis and metastasis of hepatocellular carcinoma via the miR-200a-3p/ZEB1 signaling pathway.
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.
First Central Clinical College, Tianjin Medical University, Tianjin, P.R. China.
Shi-Peng
SP
Li
Department 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.
Hai-Xu
HX
Xu
First Central Clinical College, Tianjin Medical University, Tianjin, P.R. China.
Yao
Y
Yu
First Central Clinical College, Tianjin Medical University, Tianjin, P.R. China.
Jin-Dan
JD
He
First Central Clinical College, Tianjin Medical University, Tianjin, P.R. China.
Zhen
Z
Wang
First Central Clinical College, Tianjin Medical University, Tianjin, P.R. China.
Yan-Jie
YJ
Xu
Department 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.
Chang-Ying
CY
Wang
First Central Clinical College, Tianjin Medical University, Tianjin, P.R. China.|Oriental Organ Transplant Center of Tianjin First Central Hospital, Key Laboratory of Organ Transplantation of Tianjin, Tianjin, P.R.China.
Hai-Ming
HM
Zhang
Laboratory 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.
Rong-Xin
RX
Zhang
First Central Clinical College, Tianjin Medical University, Tianjin, P.R. China.|Oriental Organ Transplant Center of Tianjin First Central Hospital, Key Laboratory of Organ Transplantation of Tianjin, Tianjin, P.R.China.
Jian-Jun
JJ
Zhang
Department 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.
Zhi
Z
Yao
First Central Clinical College, Tianjin Medical University, Tianjin, P.R. China.|Oriental Organ Transplant Center of Tianjin First Central Hospital, Key Laboratory of Organ Transplantation of Tianjin, Tianjin, P.R.China.
Zhong-Yang
ZY
Shen
D000111:Acetylcysteine / Q000378:metabolism; D000368:Aged; D000818:Animals; D017209:Apoptosis; D063646:Carcinogenesis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D062085:RNA, Long Noncoding / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000235:genetics / Q000378:metabolism*
C574685:HULC long non-coding RNA, human; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D000111:Acetylcysteine
ZEB1; epithelial-mesenchymal transition; hepatocellular carcinoma; lncRNA HULC; miR-200a-3p