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 article is part of a series of apparently falsifications produced by papermills. This is seen by the typical article setup and characteristic Western immunoblots with diffuse bands and repetitive patterns in the background between individual blots (seen when increasing the contrast). This is seen in e.g. Figure 5f and g (not so clear) and Figure 1c.  , 
 #1 Original thread here: https: pubpeer.com publications 9387E3A39647973106A393430D081D# , 
 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: 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. , 
 From the Ministry of Science and Technology of the People s Republic of China:  [Results of the investigation and handling of medical research integrity cases in some educational and medical institutions](http: www.most.gov.cn zxgz kycxjs kycxgzdt 202203 t20220318_179892.html) (March 17, 2022) . Thanks Google Translate. ------------------ 21.  KRas-ERK signalling promotes the onset and maintenance of uveal melanoma through regulating JMJD6-mediated H2A.X phosphorylation at tyrosine 39  . After investigation, it was found that the paper tampered with the data and invested on behalf of others. Li Yaping (merged with the other 3 papers) shall be dealt with as follows: Circulate criticism, cancel the application qualification for scientific and technological plan projects (special projects, funds, etc.) for 8 years, cancel the qualification for various awards and evaluation for 2 years, cancel the effective declaration of job title and professional title promotion Qualification once, post allowance deducted for 24 months, and prohibited from participating in postgraduate admissions qualification review for 2 years; Han Ning will be dealt with as follows: Circulate criticism, cancel the application qualification for scientific and technological projects (special projects, funds, etc.) for 5 years, and cancel various awards and evaluations Excellent qualification for 2 years, cancellation of post, title promotion valid for 1 time, deduction of post allowance for 12 months, prohibition from participating in postgraduate admissions qualification review for 1 year; Sun Weixuan (merged with the other 3 papers) will be dealt with as follows: as a current graduate student , to be given a school probation sanction. u3000u3000(Notification link: http: jluxfjs.jlu.edu.cn content.jsp?urltype=news.NewsContentUrl wbtreeid=1021 wbnewsid=1453) ,