Gluconokinase IDNK Promotes Cell Proliferation and Inhibits Apoptosis in Hepatocellular Carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) is one of the deadliest cancers globally with a poor prognosis. Breakthroughs in the treatment of HCC are urgently needed. This study explored the role of IDNK in the development and progression of HCC. METHODS: IDNK expression was suppressed using short hairpin (shRNA) in BEL-7404 and Huh-7 cells. The expression of IDNK in HCC cells after IDNK knockdown was evaluated by real-time quantitative RT-PCR analysis and Western blot. After IDNK silencing, the proliferation and apoptosis of HCC cells were evaluated by Celigo cell counting, flow cytometry analysis, MTT assay, and caspase3/7 assay. Gene expressions in BEL-7404 cells transfected with IDNK shRNA lentivirus plasmid and blank control plasmid were evaluated by microarray analysis. The differentially expressed genes induced by deregulation of IDNKwere identified, followed by pathway analysis. RESULTS: The expression of IDNK at the mRNA and protein levels was considerably reduced in shRNA IDNK transfected cells. Knockdown of IDNK significantly inhibited HCC cell proliferation and increased cell apoptosis. A total of 1196 genes (585 upregulated and 611 downregulated) were differentially expressed in IDNK knockdown BEL-7404 cells. The pathway of tRNA charging with Z-score = -3 was significantly inhibited in BEL-7404 cells with IDNK knockdown. CONCLUSION: IDNK plays a key role in the proliferation and apoptosis of HCC cells. IDNK may be a candidate therapeutic target for HCC.

Over-expression of ASIC1a promotes proliferation via activation of the ß-catenin/LEF-TCF axis and is associated with disease outcome in liver cancer.

Acid-sensing ion channels 1a (ASIC1a) has been reported to promote migration and invasion in liver cancer. However, the clinical significance and molecular mechanism of ASIC1a in liver cancer remain unknown. In the study, we found that ASIC1a is frequently up-regulated in liver cancer tissues. The over-expression of ASIC1a is associated with advanced clinical stage and poor prognosis. The pro-proliferative of ASIC1a is pH dependent. Knockout of ASIC1a by CRISPR/CAS9 inhibited liver cancer cell proliferation and tumorigenicity in vitro and in vivo through ß-catenin degradation and LEF-TCF inactivation. Our results indicated a potential diagnostic marker and chemotherapeutic target for liver cancer.