PHD2 acts as an oncogene through activation of Ras/Raf/MEK/ERK and JAK1/STAT3 pathways in human hepatocellular carcinoma cells
Authors: Junqiang Guo
Zhi Lan
Journal: Artificial Cells Nanomedicine and Biotechnology (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: HepG3B cell; Huh7 cell; invasion; migration; proliferation.
Affiliations: Department of Trauma Emergency, Huaihe Hospital, Henan University, Kaifeng, China., Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Abstract:  Background: Prolyl hydroxylase domain proteins (PHD2) is an oxygen sensor that is able to induce hypoxia-inducible factor-α (HIF-α) degradation under normoxic condition. The present paper designed to reveal the function of PHD2 in hepatocellular carcinoma (HCC) cells proliferation, migration and invasion.Methods: qRT-PCR and Western blot were carried out to see the expression of PHD2 in HCC tissues and cell lines. PHD2 expression in Huh7 and HepG3B cells was overexpressed or suppressed by transfection and then the changes of cell proliferation, migration and invasion were detected by CCK-8 assay, transwell assay and Western blot.Results: PHD2 was highly expressed in HCC tissues and cell lines (Huh7, Hep3B, SK-HEP-1, HCCLM3 and MHCC97) as relative to para-cancerous non-tumour tissues and a normal hepatocyte line MIHA. PHD2 overexpression promoted Huh7 and Hep3B cells viability, migration and invasion. Meanwhile, CyclinD1, c-Myc, MMP-2, MMP-9 and Vimentin were up-regulated, while p53 was down-regulated by PHD2 overexpression. PHD2 silence led to a contrary impact. Further, PHD2 overexpression up-regulated Ras and Raf expression and induced phosphorylation of MEK, ERK, JAK1 and STAT3.Conclusion: PHD2 exhibited pro-tumour functions in HCC cells. PHD2 promoted HCC possibly through Ras/Raf/MEK/ERK and JAK1/STAT3 pathways.HighlightsPHD2 is highly expressed in HCC tissue and cell lines;PHD2 promotes the proliferation of Huh7 and HepG3B cells;PHD2 enhances Huh7 and HepG3B cells migration and invasion;PHD2 activates Ras/Raf/MEK/ERK and JAK1/STAT3 signalling. 

Retracted: No

PubPeer comments:
  Figure 4. PHD2 enhanced Huh7 and Hep3B cells migration and invasion. A PHD2 expressing plasmid (pEX-PHD2) and two glasses of specific shRNA against PHD2 (sh-PHD2#1 and sh-PHD2#2) were transfected into Huh7 and Hep3B cells. Migration of (A) Huh7 and (B) Hep3B cells was tested by Transwell assay. Invasion of (C) Huh7 and (D) Hep3B cells was tested by Transwell assay ![file] Two pairs of panels are duplicates. , 
 This paper belongs to a set of over 400 papers (as per February 2020) that share very similar Western blots with tadpole-like shaped bands, the same background pattern, and striking similarities in title structures, paper layout, bar graph design, and - in a subset - flow cytometry panels. Despite these similarities, these papers are authored by researchers from different departments and institutes, with almost no overlap in authors. The list of these papers is available here: https: docs.google.com spreadsheets d 1KXqTAyl4j-jVorFPMD2XRpr76LcIKJ0CVyIvRj0exYQ edit?usp=sharing A more detailed description of this set of papers, suspected to all be generated by a common source, a paper mill , can be found here: * https: forbetterscience.com 2020 01 24 the-full-service-paper-mill-and-its-chinese-customers (January 2020) * https: scienceintegritydigest.com 2020 02 21 the-tadpole-paper-mill (February 2020) The same paper mill has been described in these papers: * Jana Christopher - Systematic fabrication of scientific images revealed - FEBS Letters (2018) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13201 * Jennifer A Byrne and Jana Christopher - Digital magic, or the dark arts of the 21st centuryu2014how can journals and peer reviewers detect manuscripts and publications from paper mills? - FEBS Letters (2020) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13747 , 
 Expression of Concern published on Mar. 17, 2020 https: www.tandfonline.com doi full 10.1080 21691401.2020.1741861 We, the Publisher and Editor of Artificial Cells, Nanomedicine, and Biotechnology, are issuing an Expression of Concern for the following article: Article title: PHD2 acts as an oncogene through activation of Ras Raf MEK ERK and JAK1 STAT3 pathways in human hepatocellular carcinoma cells Authors: Junqiang Guo and Zhi Lan Journal: Artificial Cells, Nanomedicine, and Biotechnology Bibliometrics: Volume 48, Number 01, pages 37u201345 DOI: https: doi.org 10.1080 21691401.2019.1699806 After publication of this article, questions about the scientific integrity of the article content were brought to the Publisher and Editoru2019s attention. We have reached out to the authors requesting that they supply information that would confirm the articleu2019s integrity, but the authors have not responded to our queries within the requested timeframe. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. , 
 **Retracted** February 3, 2022 u201cWe, the Editors and Publisher of the journal Artificial Cells, Nanomedicine, and Biotechnology, have retracted the following article: Junqiang Guo Zhi Lan (2020) PHD2 acts as an oncogene through activation of Ras Raf MEK ERK and JAK1 STAT3 pathways in human hepatocellular carcinoma cells. Artificial Cells, Nanomedicine, and Biotechnology, 48(1), 37u201345, DOI: 10.1080 21691401.2019.1699806 Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors have been unable to verify their original data or answer our questions about research ethics and the informed consent process. We are therefore retracting this article and the corresponding author listed in this publication has been informed. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. u201c , 
 The subject of [an investigation by Henan University] . H t Google Translate. ------------------ In order to strengthen the construction of scientific research integrity, severely punish violations, and create a good environment for scientific and technological innovation , the relevant paper issues recently investigated and dealt with by this unit are hereby notified as follows. 1. Guo Junqiang, Huaihe Hospital of Henan University, purchased SCI papers. After investigation, Li Shijie is the corresponding author, Guo Junqiang and Yang Zhijia are the first authors of the paper  LncRNA SNHG16 functions as an oncogene by sponging miR-200a-3p in pancreatic cancer , Guo Junqiang is the corresponding author and the first author of the paper ** PHD2 acts as an oncogene through activation of Ras Raf MEK ERK and JAK1 STAT3 pathways in human hepatocellular carcinoma cells **, which was purchased and written by Guo Junqiang through a third party, and at the same time violated the authorship specification, without the knowledge of other authors, Li Shijie Sign up as a corresponding author, and sign other colleagues as co- or participating authors. Henan University will deal with the relevant responsible persons as follows: Guo Junqiang will be given a warning, a scientific research admonishment, and an order to withdraw the manuscript. The whole school will notify the criticism, and the paper layout fee will be recovered; the qualification for promotion of the professional title will be postponed for 2 years; ), science and technology awards, qualifications for the title of scientific and technological talents, qualifications for evaluation and evaluation, nomination or recommender, nominee or recommender, evaluation expert and other qualifications for 5 years. Give Li Shijie and Yang Zhijia scientific research integrity admonitions, the whole school will report criticism, and cancel the qualification for evaluation for one year. ,