CARMA3/NF-Œ∫B signaling contributes to tumorigenesis of hepatocellular carcinoma and is inhibited by sodium aescinate
Authors: Hui Hou
Xiao-Ping Geng
Xiao Cui
Da-Chen Zhou
Wei-Xiang Li
Bin Zhang
Journal: World journal of gastroenterology (2019)
Discipline: CLINICAL MEDICINE
Keywords: CARMA3; Hepatocellular carcinoma; Liver cancer; Nuclear factor kappa-B; Sodium aescinate
Affiliations: We-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., Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, United States., Department of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui Province, China. .

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 &lt; 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-Œ∫B) 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-Œ∫B. SA inhibits HCC growth by targeting CARMA3/NF-Œ∫B. 

Retracted: No

PubPeer comments:
 From the methods:  Tumor tissues and paired adjacent liver tissues were obtained from 100 HCC patients who had undergone liver resection at the First Affiliated Hospital of Anhui Medical University and the Second Hospital of Anhui Medical University between 2000 and 2015 (100 pairs of HCC tumor tissues and adjacent liver tissues, randomly selected from an HCC tissue bank of 527 patients). (....). The deadline of this research was June 30, 2017. If some samples were obtained in 2015 and the deadline was 2017, how can all patients have been followed for 100 to 150 months (8 to 12 years), as shown in Figures 1A and B?  , 
 Figure 2. * Pink boxes: Two panels appear to look very similar.  , 
 #1 Thanks for your question. We have our own clinical tissue bank in our research center. The collection of tissue is from 2004. We can supply the original data of the tissue bank. The longest survival time of the included patients is 150 month, so we say that the longest follow-up time is 150 month. Our bad English writing caused this misunderstand. #2 The tissue IHC staining was conducted with the Tissue microarray slides. Four TMA slides were made based on the tissue bank as described in the article. In figure 2, the images of 5u00d7 and 20u00d7 from the same tissue slide were shown. Unintentional mistaking was done when uploading the u2018TIFu2019 figures in the system. From figure 2, we can check from the 5u00d7 images that both 20u00d7 images were the same and from the same 5u00d7 image of NFKB in figure 2. I checked the original files for uploading, the original figure is shown here. , 
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