Retracted : Carcinogenic role of K‚ÄêRas‚ÄêERK1/2 signaling in bladder cancer via inhibition of H1.2 phosphorylation at T146
Authors: Xin Wei
Li Fan
Weihua Wang
Yao Wang
Journal: Journal of Cellular Physiology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: DNA-PK; H1.2 phosphorylation; K-Ras-ERK signaling; MDM2; bladder cancer.
Affiliations: Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, China.

Abstract:  It has been reported that Ras-ERK signaling regulated tumor suppressive genes via epigenetic mechanisms. Herein, we set out to investigate the correlation between K-Ras-ERK1/2 signaling and H1.2 phosphorylation, to provide a better understanding of K-Ras-ERK signaling in cancer. A plasmid for expression of mutated K-Ras was transfected into human bladder carcinoma HT1197 cells. Western blot was carried out for testing the expression changes of ERK1/2 and H1.2. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, soft-agar colony formation assay, and transwell assay were used to test the effects of H1.2 phosphorylation at T146 (H1.2 T146ph ) on HT1197 cells growth and migration. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and chromatin immunoprecipitation (ChIP) were performed to test whether H1.2 T146ph regulated K-Ras-ERK1/2 downstream genes. Furthermore, how K-Ras-ERK1/2 regulated H1.2 T146ph expression was studied. We found that the ERK1/2 was activated when K-Ras was mutated, and H1.2 T146ph expression was significantly downregulated by K-Ras mutation. H1.2 T146E for mimicking H1.2 T146ph significantly attenuated K-Ras mutation induced increases in HT1197 cells viability, colony formation, and relative migration. Besides, H1.2 T146ph regulated the transcription of K-Ras-ERK1/2 downstream genes, including NT5E, GDF15, CARD16, CYR61, IGFBP3, and WNT16B. Furthermore, K-Ras-ERK1/2 signaling inhibited H1.2 phosphorylation at T146 through degradation of DNA-PK, and the degraded DNA-PK by K-Ras-ERK1/2 possibly via modulation of MDM2. In conclusion, the activation of K-Ras-ERK1/2 signaling will repress the phosphorylation of H1.2 at T146, and thereby, promoted the growth and migration of bladder cancer cells. K-Ras-ERK1/2 signaling repressed H1.2 phosphorylation possibly by MDM2-mediated degradation of DNA-PK. 

Retracted: Yes

PubPeer comments:
 The Western blots and other figures in this paper have an interesting layout that appears to be shared with many other papers, as discussed in a January 2020 post on Leonid Schneider s blog: https: forbetterscience.com 2020 01 24 the-full-service-paper-mill-and-its-chinese-customers The list of these papers is available here: https: docs.google.com spreadsheets d 1KXqTAyl4j-jVorFPMD2XRpr76LcIKJ0CVyIvRj0exYQ edit?usp=sharing In almost all papers, Western blot panels within the same figure, and across figures and papers, appear to share the same background, while the bands are regularly spaced, all have similar rounded edges without the usual smudges and specks, and with some bands showing a recognizable  jumping sardine shape. Also in almost all papers, bar graphs show a characteristic layout with bars in solid shades of grey, and the left-most bar in black, as well as double-edged error bars. Many papers have  cell viability and  apoptotic cells graphs. To illustrate the recognizable layout of the graphs in this paper, here is Figure 4.  , 
 Retracted [8 June 2021] . --------------------------------- The above article, published online on 29 April 2019 in Wiley Online Library , has been retracted by agreement between the journal s Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC The retraction has been agreed following an investigation based on allegations raised by a third party. Several flaws and inconsistencies between results presented and experimental methods described were found, the editors consider the conclusions of this article to be invalid. The authors collaborated in the investigation initially, but were not available for a final confirmation of the retraction. , 
 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. -------------------------------------------------------- 19.  Carcinogenic role of K-Ras-ERK1 2 signaling in bladder cancer via inhibition of H1.2 phosphorylation at T146 by Wei Xin as the corresponding author and Fan Li as the first author from the Sino-Japanese Friendship Hospital of Jilin University. After investigation, the paper has the behavior of buying and selling paper data. Fan Li (merged with the other 2 articles) shall be dealt with as follows: Circulate criticism, cancel the application qualification for scientific and technological plan projects (special projects, funds, etc.) for 6 years, cancel the qualification for various awards and evaluations for 2 years, cancel the position, and the promotion of professional title is effective Apply for qualification once, withhold post allowance for 24 months, prohibit participation in postgraduate admissions qualification review for 2 years, revocation of doctoral degree; for Wei Xin (merged with the other 2 papers), the following treatment will be made: Circulate criticism, cancel science and technology project (special project) , funds, etc.) for 5 years, cancel the qualifications for various awards and evaluations for 2 years, cancel the valid application qualification for job title promotion once, withhold the post allowance for 12 months, and prohibit participating in the postgraduate admissions qualification review for 1 year. u3000u3000(Notification link: http: jluxfjs.jlu.edu.cn content.jsp?urltype=news.NewsContentUrl wbtreeid=1021 wbnewsid=1441) ,