Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 28, 2019; 25(36): 5483-5493
Published online Sep 28, 2019. doi: 10.3748/wjg.v25.i36.5483
CARMA3/NF-κB signaling contributes to tumorigenesis of hepatocellular carcinoma and is inhibited by sodium aescinate
Hui Hou, Wei-Xiang Li, Xiao Cui, Da-Chen Zhou, Bin Zhang, Xiao-Ping Geng
Hui Hou, Wei-Xiang Li, Xiao Cui, Da-Chen Zhou, Bin Zhang, Xiao-Ping Geng, Department of General Surgery, The Second Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
Xiao Cui, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, United States
Xiao-Ping Geng, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui Province, China
Author contributions: Hou H wrote the paper and performed the operations and pathological test; Li WX and Zhou DC performed molecular experiments; Cui X and Zhang B analyzed the data; Geng XP designed the experiments and reviewed the manuscript; Hui H, Li WX, and Cui X contributed equally to this work.
Supported by the Nature Science Foundation of High Education Institution of Anhui Province, No. KJ2017A825; Anhui Provincial Natural Science Foundation, No. 1808085MH270; Foundation of the Higher Education Institution of Henan Province, No. 16A320007; “ Huohua Jihua” Foundation of the Second Hospital of Anhui Medical University Science, No. 2015hhjh05; and Anhui Medical University Science Foundation, No. 2017xkj033.
Institutional review board statement: This study was approved by the Ethics Committee of The Second Affiliated Hospital.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: No additional unpublished data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Xiao-Ping Geng, MD, Director, Professor, Department of Hepato-Pancreato-Biliary Surgery, Department of Surgery, The second hospital of Anhui Medical University, Furong Road, 678#, Hefei 230601, Anhui Province, China. xp_geng@163.net
Telephone: +86-551-63869594 Fax: +86-551-63869594
Received: June 17, 2019
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
Abstract
BACKGROUND

Primary hepatocellular carcinoma (HCC) is a very malignant tumor in the world. CARMA3 plays an oncogenic role in the pathogenesis of various tumors. However, the function of CARMA3 in HCC has not been fully clarified.

AIM

To study the biological function of CAEMA3 in HCC.

METHODS

Tissue microarray slides including tissues form 100 HCC patients were applied to access the expression of CARMA3 in HCC and its clinical relevance. Knockdown and overexpression of CARMA3 were conducted with plasmid transfection. MTT, colony formation, and apoptosis assays were performed to check the biological activity of cells.

RESULTS

Higher expression of CARMA3 in HCC was relevant to poor prognostic survival (P < 0.05). Down-regulation of CARMA3 inhibited proliferation and colony formation and induced apoptosis in HCC cell lines, while increasing its expression promoted tumorigenesis. We also found that sodium aescinate (SA), a natural herb extract, exerted anti-proliferation effects in HCC cells by suppressing the CARMA3/nuclear factor kappa-B (NF-κB) pathway.

CONCLUSION

Overexpression of CARMA3 in HCC tissues correlates with a poor prognosis in HCC patients. CARMA3 acts pro-tumorigenic effects partly through activation of CARMA3/NF-κB. SA inhibits HCC growth by targeting CARMA3/NF-κB.

Keywords: CARMA3, Nuclear factor kappa-B, Sodium aescinate, Hepatocellular carcinoma, Tumorigenesis, Liver cancer

Core tip: Hepatocellular carcinoma (HCC) ranks the sixth in the most common malignant tumors and is the most frequent primary liver cancer; the nuclear factor kappa-B (NF-κB) signal pathway is commonly activated and exerts critical roles in the progression of HCC. Here, we hypothesized that CARMA3 might play an oncogenic role in HCC by activating NF-κB, and explored the relationships between CARMA3 expression and clinicopathological characteristics. Furthermore, we found that sodium aescinate exerted anti-tumor effects possibly by inactivating CARMA3/NF-κB signaling.