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 ... -  《-》

A novel lncRNA MCM3AP-AS1 promotes the growth of hepatocellular carcinoma by targeting miR-194-5p/FOXA1 axis.

Wang Y ，Yang L ，Chen T ，Liu X ，Guo Y ，Zhu Q ，Tong X ，Yang W ，Xu Q ，Huang D ，Tu K ... -  《Molecular Cancer》

MicroRNA-98-5p Inhibits Tumorigenesis of Hepatitis B Virus-Related Hepatocellular Carcinoma by Targeting NF-κB-Inducing Kinase.

MicroRNAs play key regulatory roles in the tumorigenesis of hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). This study aimed to explore the regulatory effects of microRNA-98-5p (miR-98-5p) on the proliferation, migration, invasion, and apoptosis of HBV-HCC cells, as well as the underlying mechanisms involving nuclear factor-κB-inducing kinase (NIK). The expressions of miR-98-5p and NIK in HBV-HCC tissues and cells, and the level of HBV DNA in HBV-HCC cells were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, migration, invasion, and apoptosis of HBV-HCC cells were analyzed by cell counting kit-8, wound healing, transwell, and flow cytometry assay, respectively. The targeting relationship between miR-98-5p and NIK was predicted by StarBase3.0 and verified by dual-luciferase reporter assay. HBV-HCC xenograft tumor model was constructed in mice to observe the tumor growth in vivo. The expression of miR-98-5p was declined in HBV-HCC tissues and cells. Overexpression of miR-98-5p markedly reduced the level of HBV DNA; inhibited the proliferation, migration, and invasion; and promoted the apoptosis of HBV-HCC cells. NIK was a target of miR-98-5p. Overexpression of miR-98-5p markedly decreased the protein expression of NIK in MHCC97H-HBV cells. NIK reversed the tumor-suppressing effect of miR-98-5p on HBV-HCC cells. Furthermore, overexpression of miR-98-5p significantly inhibited the xenograft tumor growth and decreased the expression of NIK in mice. MiR-98-5p inhibits the secretion of HBV, proliferation, migration, and invasion of HBV-HCC cells by targeting NIK.

Fei X ，Zhang P ，Pan Y ，Liu Y ... -  《-》

Hepatitis B virus X protein related lncRNA WEE2-AS1 promotes hepatocellular carcinoma proliferation and invasion.

Hepatitis B virus X protein (HBx) is involved in the initiation and progression of hepatocellular carcinoma (HCC) by regulating the host protein-coding genes. In this study, we showed that HBx altered the expression of lncRNAs to promote the progression of HCC. lncRNA microarray and quantitative reverse-transcription polymerase chain reactions (qRT-PCRs) were performed to identify lncRNAs that were differentially regulated by HBx in HCC cells and tissues. Protein, mRNA, and lncRNA expression analyses; cell cycle and apoptosis analyses; loss/gain-of-function analysis were performed to delineate the consequences of WEE2-AS1 upregulation in HCC cells. WEE2-AS1 over-expressed in HCC and was positively correlated to hepatitis B virus (HBV) infection, hepatic vascular invasion, poor tumor differentiation and poor patient prognosis. WEE2-AS1 also accelerated the proliferation, migration, invasion and cell cycle progression of HCC cells. Fermitin family member 3 (FERMT3) was a downstream target of WEE2-AS1. In conclusion, there is a preliminary HBx-WEE2-AS1- FERMT3 pathway which may serve as a therapeutic target for HBV-associated HCC.

Hu Z ，Huang P ，Yan Y ，Zhou Z ，Wang J ，Wu G ... -  《-》

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 ... -  《-》