Published online Sep 28, 2019. doi: 10.3748/wjg.v25.i36.5483
Peer-review started: June 18, 2019
First decision: August 3, 2019
Revised: August 13, 2019
Accepted: August 24, 2019
Article in press: August 24, 2019
Published online: September 28, 2019
Hepatocellular carcinoma (HCC) is one of the deadliest malignant tumors in the world. The incidence rate of HCC continuously rises over the last decades. The therapeutic effects are still unsatisfied.
As an oncogenic factor, CARMA3 has been explored in various types of tumors. The role of CARMA3 in the tumorigenesis of HCC and its potential therapeutic application have not been fully identified.
To investigate the biological function of CARMA3 in the progression of HCC, and the potential therapeutic effects of sodium aescinate (SA) in HCC.
TMA slides with paraffin-embedded HCC samples from 100 patients were employed in this study. Expression of CARMA3 in HCC tissues was detected by immunohistochemistry (IHC). The biological function of CARMA3 in HCC was investigated by increasing or decreasing endogenous CARMA3 expression in HepG2 and Hep3B cells using plasmid transfection in vitro. The proliferation and colony formation assays and apoptosis detection kits were used to investigate the role of CARMA3 and SA in HCC cells. Western blot and immunofluorescence assays were used to detect the expression of targeted proteins.
IHC analysis showed that CARMA3 was increased in HCC tissues compared with adjacent non-cancerous liver tissues. High CARMA3 expression in HCC predicted less overall survival time and disease-free survival time in HCC patients. Knockdown of CARMA3 expression inhibited proliferation and colony formation, and induced early apoptosis in HCC cells. Increasing endogenous CARMA3 expression in HCC cells promoted cell growth and suppressed apoptosis. SA inhibited the growth of HCC cells and decreased the expression of CARMA3 and its targeted protein nuclear factor kappa-B (NF-κB). No anti-proliferation or pro-apoptosis effect was observed in human hepatocytes treated with SA.
Expression of CARMA3 increases in HCC tissues and correlates with a poor prognosis in HCC patients. CARMA3 acts pro-tumorigenic effects by enhancing HCC growth and inhibiting apoptosis partly through activation of CARMA3/NF-κB. SA inhibits HCC growth by targeting CARMA3/NF-κB.
Our work gave an insight of the mechanism of CARMA3 in the pathogenesis of HCC and explored its potential therapeutic application for HCC, which provide a promising target for HCC treatment.