Downregulation of miR-1225-5p is pivotal for proliferation, invasion, and migration of HCC cells through NFκB regulation.

BACKGROUND: As one of the most frequently seen malignancies, hepatocellular carcinoma (HCC) serves as the second largest contributor to malignancy-specific mortality worldwide. MicroRNA-1225-5p (miR-1225) exerts an essential impact on the growth and metastasis of many malignancies. However, the contribution of miR-125 to HCC and the molecular mechanism of cancer cell viability and apoptosis are still unclear. We focused our research on exploring the function and molecular mechanism of miR-1225 in regulating HCC cell growth, migration, and invasion. MATERIAL: Quantitative PCR data showed that miR-1225 expression was repressed in HCC cell lines and in the tissues of HCC patients, compared to that in normal human hepatic cells and tissues. Transfection of a miR-1225 mimic inhibited cell viability and proliferation as indicated by CCK-8 staining and MTT assay. Transwell invasion, wound healing assay, and Western blotting were performed to assess whether miR-1225 repressed the metastasis and invasion of HCC cells, and decreased matrix metalloproteinase 9 (MMP9) expression. Further bioinformatic prediction and dual-luciferase reporter assay suggested that miR-1225 targeted the 3'-UTR of NFκB p65. RESULTS: Overexpression of p65 protein counteracted the repressive impact of miR-1225 on invasion, migration, and proliferation of HCC cells. CONCLUSION: This research provided new evidences that miR-1225 inhibits the viability, migration, and invasion of HCC cells by downregulation of p65.

The long noncoding RNA cardiac hypertrophy-related factor plays oncogenic roles in hepatocellular carcinoma by downregulating microRNA-211.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most major type of primary hepatic cancer. This study aimed to explore the possible oncogenic effects of the long noncoding RNA cardiac hypertrophy-related factor (CHRF) on HCC, as well as the underlying possible mechanism. METHODS: The expression levels of CHRF and microRNA-211 (miR-211) in HCC tissues and/or cell lines HepG2 and Huh-7 were measured using quantitative reverse transcription polymerase chain reaction. Cell transfection was conducted to change the expression levels of CHRF and miR-211 in cells. Cell viability and apoptosis were assessed using the cell counting kit-8 assay and annexin V-phycoerythrin staining, respectively. The pull-down assay and RNA immunoprecipitation were performed to analyze the association between CHRF and miR-211. The expression of the key factors involving in cell proliferation, cell apoptosis, and epithelial-mesenchymal transition (EMT) process, as well as the phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) and Wnt/ß-catenin pathways, were evaluated by Western blot analysis. RESULTS: CHRF was highly expressed in HCC tissues and positively associated with the TNM stage, differentiation, and size of tumors. Overexpression of CHRF promoted HepG2 cell viability, proliferation, and EMT process. CHRF knockdown had opposite effects. Moreover, CHRF negatively regulated the expression of miR-21, and miR-21 was a direct target of CHRF. Overexpression of miR-211 reversed the effects of CHRF on HepG2 and Huh-7 cell viability, proliferation, and EMT process. Furthermore, overexpression of CHRF activated the PI3K/AKT and Wnt/ß-catenin pathways in HepG2 cells by downregulating miR-211. CONCLUSION: CHRF played oncogenic roles in HCC. The overexpression of CHRF promoted HepG2 and Huh-7 cell viability, proliferation, and EMT process by downregulating miR-211 and then activating the PI3K/AKT and Wnt/ß-catenin pathways.

Drug effect analysis of sorafenib combined with transcatheter arterial chemoembolization in the treatment of advanced hepatocellular carcinoma.

Sorafenib is a new multi-target oral drug that inhibits many kinds of protein kinase small molecules to treat tumors. Currently, sorafenib is one of the drugs that permit systemic treatment of liver cancer in the middle stage. Although sorafenib has good therapeutic effect on liver cancer, the clinical effect of sorafenib alone in the treatment of liver cancer is limited. This study compared the efficacy of sorafenib, TACE (transcatheter arterial chemoembolization), and sorafenib combined with TACE in the treatment of liver cancer patients. The results showed that the curative effect of sorafenib combined with transcatheter arterial chemoembolization is better than that of hepatic artery chemoembolization or sorafenib orally. The total effective rate of combined treatment is 93.8%, while the effective rate of arterial chemoembolization and sorafenib is 64.1% and 72.2% respectively. Combined treatment can significantly prolong the total survival of the patients with liver cancer, which is significantly different from that of arterial chemoembolization or sorafenib alone.