Abstract
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 β-catenin degradation and LEF-TCF inactivation. Our results indicated a potential diagnostic marker and chemotherapeutic target for liver cancer.
Highlights
Liver cancer is commonly diagnosed and is identified as the leading causes of cancer death worldwide, with 466100 estimated new cases and 422100 estimated deaths in China and 28410 estimated new cases and 18280 estimated deaths in the United States [1, 2]
ASIC1a was found significantly up-regulated in tumor tissues and ASIC1a expression in liver cancer increased with advanced clinical stage (Figure 1A and 1B)
The findings of the current study showed that both mRNA and protein levels of ASIC1a are over-expressed in liver cancer tissues compared with adjacent normal tissues
Summary
Liver cancer is commonly diagnosed and is identified as the leading causes of cancer death worldwide, with 466100 estimated new cases and 422100 estimated deaths in China and 28410 estimated new cases and 18280 estimated deaths in the United States [1, 2]. Several lines of evidence showed that multiple proteins are deregulated in liver cancer and have been developed as biomarkers or chemotherapy targets such as AFP, PDGF and VEGFR. More research into the underlying molecular mechanisms of liver cancer tumorigenesis and the identification of de novo biomarkers and specific molecular targets is required urgently. Among six identified subunits of ASICs, ASIC1a has become a topic of interest in research because of its important biological functions and pathological significance [8]. High rates of glucose metabolism combining with poor perfusion lead to an acid tumor microenvironment in which the pH value is around
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