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 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 H19 promotes the development of hepatitis B related hepatocellular carcinoma through regulating microRNA-22 via EMT pathway.

Li L ，Han T ，Liu K ，Lei CG ，Wang ZC ，Shi GJ ... -  《-》

Long non-coding RNA CRNDE promotes the proliferation, migration and invasion of hepatocellular carcinoma cells through miR-217/MAPK1 axis.

Hepatocellular carcinoma (HCC) is an invasive malignant tumour and the second major cause of cancer-related deaths over the world. CRNDE and miR-217 are non-coding RNAs which play critical roles in cell growth, proliferation, migration. Mitogen-activated protein kinase 1 (MAPK1) also participates in cancer cell process. Hence, this study aimed at investigating the effect of CRNDE on migration and invasion of HCC and figuring out the role of miR-217 and MAPK1 in this process. The overexpression of CRNDE was demonstrated by a microarray-based lncRNA profiling study. CRNDE expression in HCC was verified by qRT-PCR. MTT assay and BrdU staining were applied to detect cell proliferation level. Transwell assay was utilized to examine cell migration and invasiveness abilities. Wound healing assay was performed for further exploration of cell migration capacity. MiR-217 was predicted by bioinformatics. The dual luciferase reporter assay was performed to corroborate the targeting relationship between CRNDE, miR-217 and MAPK1. MAPK1, the downstream target of miR-217, was predicted using bioinformatics and was further confirmed by qRT-PCR and Western blot. The interaction between CRNDE, miR-217 and MAPK1 was studied by qRT-PCR, Western blot, MTT, BrdU, transwell assay and wound healing assay. CRNDE was up-regulated in HCC tissues and HCC cell lines. The high expression of CRNDE facilitated cell proliferation, migration and invasion, while the inhibited one affected on the contrary. MiR-217, negatively correlated with CRNDE expression, was the target of CRNDE and was more lowly expressed in HCC. With the high expression of miR-217, HCC cell proliferation, migration and invasion were suppressed. MAPK1, the possible target of miR-217, was negatively correlated with miR-217 but positively correlated with CRNDE and had the same effect in HCC formation process as CRNDE. Long non-coding RNA CRNDE promotes the proliferation, migration and invasion of HCC cells through miR-217/MAPK1 axis.

Wang H ，Ke J ，Guo Q ，Barnabo Nampoukime KP ，Yang P ，Ma K ... -  《-》