BackgroundHepatocellular carcinoma (HCC) is a high-burden cancer. The molecular mechanism of HCC has not been fully elucidated. Notably, current research has revealed a significant function for long non-coding RNAs (lncRNAs) in the prognosis of patients with HCC. Here, this study aims to construct a regulated lncRNA-mediated ceRNA network and find biological targets for the treatment of HCC.MethodsBased on the RNA expression patterns from the TCGA, we did an analysis to determine which genes were expressed differently between liver tumor tissues and noncancerous tissues. Then, using bioinformatic tools, we built a lncRNA-miRNA-mRNA ceRNA network and used GO and KEGG functional analyses on the DEmRNAs connected to ceRNA networks. The main lncRNAs in the subnetwork were chosen, and we next looked at the relationships between these lncRNAs and the clinical characteristics of patients with HCC. The prognosis-related genes and immune cells were identified using Kaplan-Meier and Cox proportional hazard analyses, and CIBERSORT was utilized to separate the 22 immune cell types. CCK8 assay was performed to measure cell viability in HCC cells after lncRNA HOTTIP modulation.ResultsDifferentially expressed mRNA and lncRNAs in HCC and paracancerous tissues were identified. There are 245 lncRNAs, 126 miRNAs, and 1980 mRNAs that are expressed differently in liver tumour tissues than in noncancerous cells. Function analysis showed that mRNAs in ceRNA network were significantly enriched in G1/S transition of mototiv cell cycle, positive regulation of cell cycle process, hepatocellular carcinoma, and cancer related pathways. CD8 T cells and T follicular helper cells had a favourable link with a 0.65 correlation coefficient. Additionally, there was a strong correlation between Eosinophils, activated NK cells, and B memory cells. Strikingly, depletion of lncRNA HOTTIP inhibited viability of HCC cells. In addition, miR-205 upregulation suppressed viability of HCC cells, while miR-205 downregulation repressed viability of HCC cells. Notably, miR-205 depletion rescued HOTTIP depletion-mediated suppression of cell viability in HCC.ConclusionA ceRNA network was created by examining the lncRNA, miRNA, and mRNA expression profiles of liver tumours from the TCGA database. LncRNA HOTTIP promoted cell viability via inhibition of miR-205 in HCC cells.
Primary hepatic carcinoma (PHC) is a leading threat to cancer patients with few effective treatment strategies. OPN is found to be an oncogene in hepatocellular carcinoma (HCC) with potential as a treating target for PHC. Fenofibrate is a lipid-lowering drug with potential anti-tumor properties, which is claimed with suppressive effects on OPN expression. Our study proposes to explore the molecular mechanism of fenofibrate in inhibiting HCC. OPN was found extremely upregulated in 6 HCC cell lines, especially Hep3B cells. Hep3B and Huh7 cells were treated with 75 and 100 μM fenofibrate, while OPN-overexpressed Hep3B cells were treated with 100 μM fenofibrate. Decreased clone number, elevated apoptotic rate, reduced number of migrated cells, and shortened migration distance were observed in fenofibrate-treated Hep3B and Huh7 cells, which were markedly abolished by the overexpression of OPN. Furthermore, the facilitating effect against apoptosis and the inhibitory effect against migration of fenofibrate in Hep3B cells were abolished by 740 Y-P, an agonist of PI3K. Hep3B xenograft model was established, followed by treated with 100 mg/kg and 200 mg/kg fenofibrate, while OPN-overexpressed Hep3B xenograft was treated with 200 mg/kg fenofibrate. The tumor growth was repressed by fenofibrate, which was notably abolished by OPN overexpression. Furthermore, the inhibitory effect of fenofibrate on the PI3K/AKT/Twist pathway in Hep3B cells and Hep3B xenograft model was abrogated by OPN overexpression. Collectively, fenofibrate suppressed progression of hepatoma downregulating OPN through inhibiting the PI3K/AKT/Twist pathway.
Primary hepatic carcinoma (PHC) is a leading threat to cancer patients with few effective treatment strategies. OPN is found to be an oncogene in hepatocellular carcinoma (HCC) with potential as a treating target for PHC. Fenofibrate is a lipid-lowering drug with potential anti-tumor properties, which is claimed with suppressive effects on OPN expression. Our study proposes to explore the molecular mechanism of fenofibrate in inhibiting HCC. OPN was found extremely upregulated in 3 HCC cell lines, especially Hep3B cells. Hep3B cells were treated with 75 and 100 µM Fenofibrate, while OPN-overexpressed Hep3B cells were treated with 100 µM Fenofibrate. Hep3B xenograft model was established, followed by treated with 100 mg/kg and 200 mg/kg Fenofibrate. OPN-overexpressed Hep3B xenograft model was established, followed by treated with 200 mg/kg Fenofibrate. Decreased clone number, elevated apoptotic rate, reduced number of migrated cells, shortened migration distance, and suppressed tumor growth in xenograft model were observed by the administration of Fenofibrate, which were markedly abolished by the overexpression of OPN. Furthermore, the inhibitory effect of Fenofibrate on the PI3K/AKT/Twist pathway in Hep3B cells and Hep3B xenograft model was abrogated by OPN overexpression. Collectively, Fenofibrate suppressed progression of hepatoma by inhibiting PI3K/AKT/Twist pathway through downregulating OPN.
Objective: Our study will explore the function and regulatory mechanism of USP36 in hepatocellular carcinoma (HCC). Methods: USP36-overexpressed and USP36-knockdown cells were established. The USP36 and Myc level were checked by Western blotting and the cell viability was checked by the MTT method. The apoptotic rate was checked by flow cytometry, while the migration was detected by the Transwell assay. A xenograft model was constructed in nude mice to explore the function of USP36 in HCC. USP36-overexpressed and USP-knockdown cells were constructed by transfecting pcDNA3.1-USP36 and siRNA-USP36 (si-USP36), respectively. Myc-overexpressed cells were constructed by transfecting pcDNA3.1-Myc. Results: Significantly declined cell viability, increased apoptotic rate, elevated number of migrated cells, downregulated Myc, and repressed tumor growth were observed in USP36-knockdown HepG2 and HUH7 cells, while opposite results were observed in USP36-overexpressed HepG2 and HUH7 cells. The expression level of Myc was positively regulated by USP36. However, the USP36 level was not regulated by Myc. Lastly, the declined cell viability, increased apoptotic rate, and elevated number of migrated cells in USP36-knockdown HepG2 cells were dramatically abrogated by the overexpression of Myc. Conclusion: USP36 facilitated the progression of hepatocellular carcinoma by upregulating Myc.
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