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.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and has a high mortality rate due to a lack of effective treatments
We found that Highly upregulated in liver cancer (HULC) was over-expressed in hepatocellular carcinoma (HCC) tissues and these levels of HULC expression were significantly higher than that observed in normal liver tissues (P< 0.001, Figure 1A)
With use of alignment prediction as a means to investigate the molecular mechanisms of long noncoding RNAs (lncRNAs) HULC in HCC cells, we found that HULC was aligned with sequences of miR-200a-3p (Figure 3E)
Summary
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and has a high mortality rate due to a lack of effective treatments. Despite advances in the diagnosis and management of HCC, the biology of this cancer remains largely unknown [3]. Recent evidence has indicated long noncoding RNAs (lncRNAs) as crucial determinants of HCC development. More recent www.impactjournals.com/oncotarget investigations have revealed that lncRNAs exert multiple functions upon a wide range of biological processes, including proliferation, apoptosis, cell migration, and cell invasion [7,8,9]. Of particular relevance to the present investigation, lncRNAs are dysregulated in different types of cancer and can exert critical effects as related to cancer biology
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