KRas-ERK signalling promotes the onset and maintenance of uveal melanoma through regulating JMJD6-mediated H2A.X phosphorylation at tyrosine 39
Authors: Ning Han
Yaping Li
Wenrui Cai
Ying Zou
Peng Yu
Weixuan Sun
Journal: Artificial Cells Nanomedicine and Biotechnology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: H2A.XY39ph; JMJD6; K-Ras-ERK signalling; MDM2; Uveal melanoma.
Affiliations: Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, PR China., Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, PR China.

Abstract:  Since DNA damage is a first incident occurred during a tumour attack, it is rational that histone H2A.X phosphorylation on tyrosine 39 (H2A.XY39ph) may act as a tumour-relevant factor. This study was aimed to test the authenticity of the hypothesis. Uveal melanoma MP65 cells were transfected for expression of KRas mutated. H2A.X phosphorylation and ERK1/2 was measured, and transwell experiment was performed to examine the consequents of H2A.XY39ph on MP65 cells developing and migration. Regulatory relationship between H2A.XY39ph and ERK1/2 downstream genes were measured. Moreover, whether JMJD6 and MDM2 are involved in H2A.X phosphorylation was studied. Mutation of Ras activated ERK1/2 signalling and inhibited H2A.X phosphorylation at Y39. Silence of H2A.XY39ph contributed to the regulation of MP65 cells growth, migration and transcription of ERK1/2 downstream genes, including CYR61, IGFBP3, WNT16B, NT5E, GDF15 and CARD16. The repressed H2A.X phosphorylation through Ras-ERK1/2 signalling might be through MDM2-mediated JMJD6 degradation. Our study suggested that Ras-ERK1/2 signalling inhibited H2A.X phosphorylation at Y39, which led to the uncontrolled developing and migration of uveal melanoma cells. In addition, H2A.X phosphorylation was mediated possibly through JMJD6 which could be degraded by MDM2. 

Retracted: No

PubPeer comments:
 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, April 2021: https: www.tandfonline.com doi full 10.1080 21691401.2021.1899411  We, the Publisher and Editor of Artificial Cells, Nanomedicine, and Biotechnology, are issuing an Expression of Concern for the following article: Yaping Li, Peng Yu, Ying Zou, Wenrui Cai, Weixuan Sun Ning Han (2019) KRas-ERK signalling promotes the onset and maintenance of uveal melanoma through regulating JMJD6-mediated H2A.X phosphorylation at tyrosine 39. Artificial Cells, Nanomedicine, and Biotechnology, 47(1), 4257u20134265, DOI: 10.1080 21691401.2019.1673764. 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. Therefore, 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. ,