In the present study, we aimed to search for dysregulated lnRNAs in Hepatocellular carcinoma (HCC) tissues, and analyze the relationship of its expression level with the clinicopathological feature and patient prognosis. The biological function of FLVCR1-AS1, the identified lncRNA, in the process of HCC development, and progression was investigated in vitro and in vivo. The underlying molecular mechanism was further explored. We determined FLVCR1-AS1 expression in HCC tissues and peri-tumor tissues by bioinformatic analysis, qRT-PCR, Northern blot and in situ hybridization. The relationship between FLVCR1-AS1 expression level and prognosis was determined by analyzing clinical samples. The effects of FLVCR1-AS1 knockdown on HCC cell proliferation, apoptosis, migration, and invasion were investigated by CCK8, FACS, and tanswell assay, respectively. Tumor xenograft model was used to determine the influence of down-regulated FLVCR1-AS1 on tumor growth and metastasis. lncRNA FLVCR1-AS1 was extremely up-regulated in HCC tissues and cell lines. FLVCR1-AS1 expression level was positively correlated with tumor severity. FLVCR1-AS1 knockdown remarkably inhibited HCC cell proliferation, migration, and invasion in vitro and in vivo while induced cell apoptosis. In mechanism, FLVCR1-AS1 acted as a competitive endogenous RNAs to sponge miR-513c which targeted the mRNA of MET for degradation. By directly sponging miR-513c, FLVCR1-AS1 increased MET expression in HCC, and then promoted HCC progression. It was demonstrated that FLVCR1-AS1 played a positive role in HCC development and progression according to the study in its mechanism, function and clinical manifestation, so that it could be expected to become a new target in HCC prevention and treatment.
The aim of the present study was to explore possible gene therapy for hilar cholangiocarcinoma by detecting the activation of the Wnt signaling pathway in 4 cholangiocarcinoma cell lines and inhibiting its expression by RNA interference (RNAi) targeting key factors of this pathway. The expression levels of the Wnt pathway-related factors, Wnt2, Wnt3, β-catenin and transcription factor 4, and its target genes, c-myc and cyclin D1, in 4 cholangiocarcinoma cell lines were detected by RT-PCR, western blotting and immunofluorescence microscopy. After transfection of siRNAs targeting Wnt2 and β-catenin into FRH0201 cells, the expression of the Wnt pathway-related factors and its target genes was again detected, and the cell cycle distribution, apoptosis and proliferation were analyzed by flow cytometry and MTT assay. Activation of the Wnt pathway and the expression of its target genes were detected in all 4 cell lines at various levels. After siRNA transfection, the expression of the target genes in the FRH0201 cells was significantly downregulated. In addition, the Wnt pathway was blocked, cell apoptosis was enhanced and cell proliferation was suppressed. In conclusion, the Wnt signaling pathway is activated in cholangiocarcinoma cells. RNAi technology targeting Wnt2 and β-catenin may be a possible gene therapy for hilar cholangiocarcinoma.
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