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 ... -  《-》

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 ... -  《-》

MicroRNA-548a-5p promotes proliferation and inhibits apoptosis in hepatocellular carcinoma cells by targeting Tg737.

Zhao G ，Wang T ，Huang QK ，Pu M ，Sun W ，Zhang ZC ，Ling R ，Tao KS ... -  《-》

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 《-》

MicroRNA-424-5p acts as a potential biomarker and inhibits proliferation and invasion in hepatocellular carcinoma by targeting TRIM29.

miRNA-424-5p (miR-424-5p) has been implicated in the development and progression of various tumors. However, the functional mechanisms of miR-424-5p in hepatocellular carcinoma (HCC) are unclear. In this study, we investigated the specific biological functions of miRNA in HCC. The expression of miR-424-5p was measured by qRT-PCR in HCC tissues and cell lines. Western blot and immunohistochemistry were used to detect the protein expression level of TRIM29. The relationship between miR-424-5p and the clinicopathological features of HCC patients was analyzed. Cell function experiments were performed to examine proliferation and invasion in HCC cells. The miRNA database was used to predict downstream target genes of miR-424-5p, which were verified by a luciferase reporter assay. Furthermore, cell and animal experiments confirmed that miR-424-5p exerts its biological function through the target gene TRIM29. miR-424-5p expression was decreased in HCC tissues and cell lines, and correlated with AFP, TNM stage, intrahepatic metastasis and poor overall survival in HCC. The upregulation of miR-424-5p inhibited cell proliferation and invasion in vitro and suppressed HCC tumor growth in vivo. TRIM29 was confirmed to be the downstream target gene of miR-424-5p. Finally, rescue experiments suggested that the upregulation of TRIM29 could rescue inhibitory effect of miR-424-5p overexpression on cell proliferation and migration. miR-424-5p is a tumor suppressor miRNA that inhibits cell proliferation and invasion via directly modulating TRIM29, which is related to cell proliferation and invasion in HCC. Thus, miR-424-5p may be a potential therapeutic and new prognostic marker for HCC.

Du H ，Xu Q ，Xiao S ，Wu Z ，Gong J ，Liu C ，Ren G ，Wu H ... -  《-》