Ras-PI3K pathway promotes osteosarcoma progression via regulating VRK1-mediated H2A phosphorylation at threonine 120
Authors: Xianlun Xu
Hao Yu
Journal: Artificial Cells Nanomedicine and Biotechnology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Osteosarcoma; Ras-PI3K pathway; VRK1; histone H2A.
Affiliations: Department of Traumatology, Jining No.1 People's Hospital, Jining, Shandong, China., Affiliated Jining No. 1 People's Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, China.

Abstract:  Background: Ras-PI3K pathway aberrant activation plays an important role in the occurrence and development of osteosarcoma. This study investigated the functions of Ras-PI3K pathway specific activation on histone H2A phosphorylation at threonine 120 (H2AT120ph) in osteosarcoma cells, along with the possible internal molecular mechanisms.Methods: Cell transfection was done to alter RasG12V/Y40C, H2AT120ph and vaccinia-related kinase 1 (VRK1) expression. Then, cell viability, proliferation, migration and cell cycle distribution were assessed, respectively. qRT-PCR was utilized to measure the VRK1 and Ras-PI3K pathway downstream genes (CYR61, IGFBP3, WNT16B, NT5E, GDF15 and CARD16) expression. Chromatin immunoprecipitation (ChIP) was conducted to evaluate the input levels of H2AT120ph and VRK1 in the promoter regions of Ras-PI3K pathway downstream genes.Results: Ras-PI3K specific activation promoted histone H2AT120ph. H2AT120ph participated in the oncogenic functions of Ras-PI3K pathway on osteosarcoma by modulating the transcription of Ras-PI3K-targeted genes. Moreover, VRK1 contributed to the Ras-PI3K specific activation-induced up-regulation of H2AT120ph and osteosarcoma progression. Ras-PI3K pathway-specific activation-induced up-regulation of H2AT120ph was achieved by up-regulation of VRK1.Conclusions: Ras-PI3K pathway activation promoted osteosarcoma progression might be via up-regulating VRK1-mediated H2AT120ph. We proposed that VRK1 and H2AT120ph could be the potential targets for osteosarcoma diagnosis and treatment.HighlightsH2AT120ph is specifically promoted by Ras-PI3K pathway activation.H2AT120ph joins in the oncogenic effects of Ras-PI3K pathway on osteosarcoma.H2AT120ph regulates the transcription of Ras-PI3K-targeted genes.VRK1 takes part in the regulatory function of Ras-PI3K pathway on H2AT120ph. 

Retracted: No

PubPeer comments:
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 #1 Original thread here: https: pubpeer.com publications EF77B04D323AC8EC6D868F34FB0DB8 , 
 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 21691401.2020.1741866 We, the Publisher and Editor of Artificial Cells, Nanomedicine, and Biotechnology, are issuing an Expression of Concern for the following article: Article title: Ras-PI3K pathway promotes osteosarcoma progression via regulating VRK1-mediated H2A phosphorylation at threonine 120 Authors: Xianlun Xu and Hao Yu Journal: Artificial Cells, Nanomedicine, and Biotechnology Bibliometrics: Volume 47, Number 01, pages 4274u20134283 DOI: https: doi.org 10.1080 21691401.2019.1687506 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. , 
 Updated Expression of Concern [6 April 2021] . ------------------------------------------------ We, the Publisher and Editor of Artificial Cells, Nanomedicine, and Biotechnology, are issuing an Expression of Concern for the following article: Xianlun Xu Hao Yu (2019) Ras-PI3K pathway promotes osteosarcoma progression via regulating VRK1-mediated H2A phosphorylation at threonine 120. Artificial Cells, Nanomedicine, and Biotechnology, 47(1), 4274u20134283, DOI: 10.1080 21691401.2019.1687506 After publication of this article, questions about the scientific integrity of the article content were brought to the Publisher and Editoru2019s attention. We reached out to the authors requesting that they supply information that would confirm the articleu2019s integrity. The authors provided several files in response to our queries, but they were unable to provide the original data in a format which satisfies our requirements to confirm the authenticity of some types of data. In particular, they were unable to provide full western blots, where the molecular weight markers are indicated. In addition, the authors did not have a record of the full blot, before cutting it into strips. u202fTherefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. The authors have been notified about this Expression of Concern. ,