Long non-coding RNA Unigene56159 promotes epithelial-mesenchymal transition by acting as a ceRNA of miR-140-5p in hepatocellular carcinoma cells.

HBV infection has been reported to be closely associated with HCC development; however, the underlying mechanisms are unclear. Emerging evidence has indicated that long non-coding RNAs (lncRNAs) play important regulatory roles in the pathogenesis and progression of cancers. To investigate the important role and mechanism of lncRNAs in the progression of HBV-related HCC, we screened lncRNAs in HBV-positive and HBV-negative HCC tissues. We identified a novel lncRNA, lncRNA-Unigene56159, which is highly expressed in HBV-related HCC tissues, and further analysis showed that this lncRNA was induced by HBV in vitro. Functionally, Unigene56159 significantly promoted cell migration/invasion and epithelial-mesenchymal transition (EMT) in HCC. Mechanistically, Unigene56159 could directly bind to miR-140-5p and effectively act as a competing endogenous RNA (ceRNA) for miR-140-5p to de-repress the expression of the target gene Slug. Collectively, our findings indicate that the Unigene56159/miR-140-5p/Slug axis contributes to HCC cell migration and invasion, which may provide novel insights into the function of lncRNA-driven hepatocarcinogenesis.

Lv J ，Fan HX ，Zhao XP ，Lv P ，Fan JY ，Zhang Y ，Liu M ，Tang H ... -  《-》

Long non-coding RNA F11-AS1 inhibits HBV-related hepatocellular carcinoma progression by regulating NR1I3 via binding to microRNA-211-5p.

Long non-coding RNAs (lncRNAs) could regulate growth and metastasis of hepatocellular carcinoma (HCC). In this study, we aimed to investigate the mechanism of lncRNA F11-AS1 in hepatitis B virus (HBV)-related HCC. The relation of lncRNA F11-AS1 expression in HBV-related HCC tissues to prognosis was analysed in silico. Stably HBV-expressing HepG2.2.15 cells were established to explore the regulation of lncRNA F11-AS1 by HBx protein, as well as to study the effects of overexpressed lncRNA F11-AS1 on proliferation, migration, invasion and apoptosis in vitro. Subsequently, the underlying interactions and roles of lncRNA F11-AS1/miR-211-5p/NR1I3 axis in HBV-related HCC were investigated. Additionally, the influence of lncRNA F11-AS1 and miR-211-5p on tumour growth and metastasis capacity of HepG2.2.15 cells were studied on tumour-bearing nude mice. Poor expression of lncRNA F11-AS1 was correlated with poor prognosis in patients with HBV-related HCC, and its down-regulation was caused by the HBx protein. lncRNA F11-AS1 was proved to up-regulate the NR1I3 expression by binding to miR-211-5p. Overexpression of lncRNA F11-AS1 reduced the proliferation, migration and invasion, yet induced apoptosis of HepG2.2.15 cells in vitro, which could be abolished by overexpression of miR-211-5p. Additionally, either lncRNA F11-AS1 overexpression or miR-211-5p inhibition attenuated the tumour growth and metastasis capacity of HepG2.2.15 cells in vivo. Collectively, lncRNA F11-AS1 acted as a modulator of miR-211-5p to positively regulate the expression of NR1I3, and the lncRNA F11-AS1/miR-211-5p/NR1I3 axis participated in HBV-related HCC progression via interference with the cellular physiology of HCC.

Deng Y ，Wei Z ，Huang M ，Xu G ，Wei W ，Peng B ，Nong S ，Qin H ... -  《-》

LncRNA n335586/miR-924/CKMT1A axis contributes to cell migration and invasion in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide and chronic hepatitis B virus (HBV) infection is a major risk factor for HCC. Emerging evidences indicate that long noncoding RNAs (lncRNAs) play a pivotal role in HCC development, but its contribution to HBV-related HCC remains largely unclear. Differentially expressed lncRNAs in HBV-related HCC tissues were identified by deep sequencing in our previous study. The function of lncRNA n335586, one of most up-regulated lncRNAs in HBV-related HCC, was characterized in the present study. We found that the expression of n335586 was significantly increased in HBV positive HCC tissues and cells and was induced by HBV in vitro. Function study indicated that lncRNA n335586 remarkably promoted HCC cells migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and metastasis in vivo. Further mechanistic studies showed lncRNA n335586 promoted HCC cells migration and invasion through facilitating the expression of its host gene CKMT1A by competitively binding miR-924. In conclusion, we demonstrated that the n335586/miR-924/CKMT1A axis contributes to HCC cell migration and invasion, which may be helpful for understanding of pathogenesis of HBV-related HCC.

Fan H ，Lv P ，Mu T ，Zhao X ，Liu Y ，Feng Y ，Lv J ，Liu M ，Tang H ... -  《-》

Long non-coding RNA SBF2-AS1 promotes hepatocellular carcinoma progression through regulation of miR-140-5p-TGFBR1 pathway.

A growing number of studies has suggested that long non-coding RNAs (lncRNAs) exert essential roles in the development and progression of hepatocellular carcinoma (HCC). However, the roles of lncRNA and its molecular mechanism in HCC are largely unknown. In the present study, the functions and molecular mechanisms of a novel lncRNA, SET-binding factor 2 (SBF2) antisense RNA1 (SBF2-AS1), were investigated in HCC tissues and cell lines. We found that the expression levels of SBF2-AS1 were significantly up-regulated in HCC tissues and correlated with poor prognosis. SBF2-AS1 knockdown could inhibit the proliferation of HCC cells and attenuate the development of HCC tumor in vivo. Moreover, wound healing and Transwell assays revealed that down-regulation of SBF2-AS1 suppressed the migration and invasion of HCC cells by modulating epithelial-mesenchymal transition (EMT) ability. Mechanistically, we observed that SBF2-AS1 served as a competing endogenous RNA (ceRNA) of miR-140-5p. Subsequently, transforming growth factor beta receptor 1 (TGFBR1) was certified as a direct target of miR-140-5p and enforcing SBF2-AS1 expression elevated TGFBR1 expression in HCC. Taken together, our study suggested that SBF2-AS1 modulated TGFBR1 through sponging miR-140-5p in HCC development and progression indicating that SBF2-AS1 might be further chosen as a potential anticancer therapeutic target and a promising prognostic biomarker for HCC.

Li Y ，Liu G ，Li X ，Dong H ，Xiao W ，Lu S ... -  《-》

Hepatitis B virus promotes proliferation and metastasis in male Chinese hepatocellular carcinoma patients through the LEF-1/miR-371a-5p/SRCIN1/pleiotrophin/Slug pathway.

Hepatocellular carcinoma (HCC) is a male-dominant cancer. Several factors may contribute to the gender difference. Recent investigations have reported that miRNAs are involved in sex-linked signaling pathways and play a critical role in the molecular pathogenesis of hepatitis B virus (HBV)-related HCC. Therefore, we speculated that some of these miRNAs might contribute to the gender differences observed in HBV-related HCC. Our results showed that miR-371a-5p was significantly upregulated in tumor tissue and serum from HCC patients and that the expression level of miR-371a-5p was related to HBV infection, sexuality, TNM stage, adjacent organ invasion and microvascular invasion. Moreover, a high level of miR-371a-5p expression predicted poor overall survival of HCC patients, and in vitro and in vivo studies revealed that the overexpression of miR-371a-5p promoted proliferation and metastasis. Mechanistic investigations suggested that miR-371a-5p was upregulated by HBV and testosterone through LEF-1. SRCIN1 was a direct target of miR-371a-5p and reversed the effects of miR-371a-5p on HCC tumorigenesis. Our results also revealed that SRCIN1 negatively regulated the expression of PTN by inhibiting the activity of NF-κB. As a hepatocyte growth factor, PTN promoted EMT-induced metastasis in vitro and in vivo through the AKT/Slug pathway. These data strongly suggested that the upregulation of miR-371a-5p played an important role in HBV-related HCC. Through the LEF-1/miR-371a-5p/SRCIN1/PTN/Slug pathway, HBV and testosterone promote the proliferation and metastasis of hepatoma cells, especially in male patients with HBV-related HCC.

Bai PS ，Hou P ，Kong Y 《-》