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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.
摘要：
在肝癌（HULC）中高度上调，一种被认为是人类肝癌关键分子的lncRNA，最近发现参与肝细胞癌（HCC）的发展和进展[1，2]。据报道,HULC可以促进肝癌的侵袭和转移,但其在HCC中的功能和作用机制尚未阐明。在这项研究中,我们发现HULC在HCC组织中异常上调，并与TNM分期相关，肝内转移,HCC复发，和术后生存率。HULC耗竭在体外和体内抑制HCC细胞系的生长和转移。此外，HULC有助于ZEB1诱导的上皮-间质转化（EMT），肿瘤侵袭和转移的要求在癌症进展中起关键作用。ZEB1的这种作用被HULCsiRNA抑制。我们得出结论，HULC作为竞争性内源性RNA（ceRNA）通过上调ZEB1介导EMT。这样,它隔离miR-200a-3p信号通路以促进HCC转移。HULC作为肝癌的癌基因发挥作用，通过诱导HCC细胞激活EMT而发挥机械作用。这种效应通过miR-200a-3p/ZEB1信号通路促进肿瘤进展和转移。这种将HULC的高表达水平与HCC细胞中的EMT联系起来的新通路的鉴定可以作为开发新的抗肿瘤疗法的基础。
