Silencing alpha-fetoprotein inhibits VEGF and MMP-2/9 production in human hepatocellular carcinoma cell
Authors: Yan Li
Wenbo Meng
Kexiang Zhu
Xun Li
Jun Yan
Hui Zhang
Jinqiu Yuan
Zhongtian Bai
Wence Zhou
Tao Liu
Yumin Li
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Alpha-fetoprotein; liver cancer; angiogenesis; cell invasion; VEGF
Affiliations: The Second Hospital of Lanzhou University, Key Laboratory of Digestive System Tumors, Gansu Province, Lanzhou, Gansu Province, China ; Special Minimally Invasive Surgery, the First Hospital of Lanzhou University, Hepatopancreatobiliary Surgery Institute of Gansu Province, Clinical Medical College Cancer Center of Lanzhou University, Lanzhou, Gansu, China., The Second Department of General Surgery, the First Hospital of Lanzhou University, Hepatopancreatobiliary Surgery Institute of Gansu Province, Clinical Medical College Cancer Center of Lanzhou University, Lanzhou, Gansu, China., Department of Immunology, Cleveland Clinic, Cleveland, Ohio, United States of America., Division of Epidemiology, School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong., The Second Hospital of Lanzhou University, Key Laboratory of Digestive System Tumors, Gansu Province, Lanzhou, Gansu Province, China.

Abstract:  Alpha-fetoprotein not only serves as a diagnostic marker for liver cancer, but also posses a variety of biological functions. However, the role of Alpha-fetoprotein on tumor angiogenesis and cell invasion remains incompletely understood. In this study, we aimed to evaluate if Alpha-fetoprotein can regulate the major angiogenic factors and matrix metalloproteinases in human liver cancer cells. Alpha-fetoprotein silencing was achieved by Stealth RNAi. Expression of Alpha-fetoprotein was examined by a full-automatic electrochemistry luminescence immunity analyzer. Expression of VEGF, VEGFR-2, MMP-9, and MMP-2 was examined by Western blot and immunocytochemistry. Apoptosis was detected by TUNEL assay. Angiogenesis was detected by in vitro angiogenesis assay kit. Silencing of Alpha-fetoprotein led to an increased apoptosis, which was associated with a decreased expression of vascular endothelial growth factor, vascular endothelial growth factor receptor 2, matrix metalloproteinases-2/9. These results suggest that Alpha-fetoprotein may play a regulatory role on angiogenesis and cell invasion during liver cancer development. 

Retracted: Yes

PubPeer comments:
 Figure 4BCD. * Some groups of cells appear to be visible multiple times within the same photo. I am hoping the authors can provide an acceptable theory for how this could have happened. * Reported to the journal in October 2015. ![file] , 
 #1 There suspect may be more. Hereu2019s 3 in the middle of C. ![file] , 
 2020 retraction. https: journals.plos.org plosone article?id=10.1371 journal.pone.0244942 Following the publication of this article [1], concerns were raised regarding the results presented in Fig 3 and Fig 4. Specifically, The u03b2-actin panel of Fig 3Ca appears similar to the u03b2-actin panel of Fig 4A when horizontally compressed and vertically stretched. The authors have explained that the same experimental controls were used for these figures. Multiple unusually repetitive clusters have been detected within Fig 4B, Fig 4C, and Fig 4D. In addition, in some areas of Fig 4B the background signal does not appear to match the background signal of the immediate surrounding area, and in some areas this background signal appears to cut off other signals at the border of the mismatching areas. The authors provided underlying data for the panels B, C, and D presented in Fig 4, and explained that the similarities between the dots are the result of the non-randomised nature of the Transwell plate micro-pores. However, the underlying data provided were not an exact match with the published panels and they did not resolve the concerns pertaining to the repetition detected in these panels. In light of the concerns affecting multiple figure panels of Fig 4 that question the integrity of these data, the PLOS ONE Editors retract this article. WM, ZL, ZB, YaL, JY, TL, JY, WZ, KZ, and YuL did not agree with the retraction. WM, ZB, JY, TL, JY, WZ, KZ, and YuL stand by the articleu2019s findings. HZ either did not respond directly or could not be reached. Reference 1.Meng W, Li X, Bai Z, Li Y, Yuan J, Liu T, et al. (2014) Silencing Alpha-Fetoprotein Inhibits VEGF and MMP-2 9 Production in Human Hepatocellular Carcinoma Cell. PLoS ONE 9(2): e90660. https: doi.org 10.1371 journal.pone.0090660 pmid:24587407 ,