RETRACTED ARTICLE: Ras-ERK1/2 signaling contributes to the development of colorectal cancer via regulating H3K9ac
Authors: Xinyu Guo
Yanfei Zhu
Huanzhou Xue
Peng Zhang
Chao Zhang
Peng Tian
Journal: BMC Cancer (2018)
Discipline: CLINICAL MEDICINE
Keywords: Colorectal cancer; ERK1/2; H3K9ac; HDAC2; PCAF
Affiliations: Department of Gastrointestinal Surgery, Zhengzhou University People's Hospital (Henan Provincial People's Hospital), Zhengzhou, 450003, China., Department of General Surgery, Wuxi People's Hospital of Nanjing Medical University, Wuxi, 214023, China., Department of General Surgery, Zhengzhou University People's Hospital (Henan Provincial People's Hospital), No.7, Weiwu Road, Zhengzhou, 450003, Henan, China. .

Abstract:  Backgrounds/aims: Ras is a control switch of ERK1/2 pathway, and hyperactivation of Ras-ERK1/2 signaling appears frequently in human cancers. However, the molecular regulation following by Ras-ERK1/2 activation is still unclear. This work aimed to reveal whether Ras-ERK1/2 promoted the development of colorectal cancer via regulating H3K9ac. Methods: A vector for expression of K-Ras mutated at G12 V and T35S was transfected into SW48 cells, and the acetylation of H3K9 was measured by Western blot analysis. MTT assay, colony formation assay, transwell assay, chromatin immunoprecipitation and RT-qPCR were performed to detect whether H3K9ac was contributed to K-Ras-mediated cell growth and migration. Furthermore, whether HDAC2 and PCAF involved in modification of H3K9ac following Ras-ERK1/2 activation were studied. Results: K-Ras mutated at G12 V and T35S induced a significant activation of ERK1/2 signaling and a significant down-regulation of H3K9ac. Recovering H3K9 acetylation by using a mimicked H3K9ac expression vector attenuated the promoting effects of Ras-ERK1/2 on tumor cells growth and migration. Besides, H3K9ac can be deacetylated by HDAC2 and MDM2-depedent degradation of PCAF. Conclusion: H3K9ac was a specific target for Ras-ERK1/2 signaling pathway. H3K9 acetylation can be modulated by HDAC2 and MDM2-depedent degradation of PCAF. The revealed regulation provides a better understanding of Ras-ERK1/2 signaling in tumorigenesis. 

Retracted: Yes

PubPeer comments:
 At top here are Figs 2C and 2D:  Subsequently, pEGFP-H3, pEGFP-K-RasG12V T35S plus pEGFP-H3, or pEGFP-K-RasG12V T35S plus pEGFP-H3K9Q (2u2009g) was transfected into cell, and **c number of colonies** and **d cell migration** were respectively determined by colony formation assay and transwell assay. Also, Fig 4D:  migration . ![file] Evidently these were not in the initially-submitted version of the paper, as we read in the [Open Peer Review records] that a reviewer requests  Representative pictures for transwell migration and soft-agar colony formation assays . The reviewer was presumably satisfied, and did not notice the overlap between panels of 2D and 4D (green boxes), casting doubt on their identification. In the lower half, I have added Figs 2C D and 3C D, nominally Colony formation and Cell invasion images for osteosarcoma cell-line cells MG63 under various conditions of tranfection (or not) with oeZIC2 or siZIC2; from [Huang Jin (2018)] . Overlaps between the two papers are marked. Also colony image reuse (after rotation). There are no authors in common. , 
 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 , 
 2021 retraction. https: bmccancer.biomedcentral.com articles 10.1186 s12885-021-08340-3 Published: 24 May 2021 The Editor in Chief retracted this article because of significant concerns regarding a number of Figures presented in this work, which question the integrity of the data. Specifically, a number of images appear to be the same and rotated between Fig. 2C, 2D and 4D in this article, and Fig. 2 and 3 in an article published earlier by unrelated authors ([1], now retracted). In addition, it appears that one image was re-used between Fig. 2D and 4D within this article. The Editor-in-Chief therefore no longer has confidence in the integrity of the data in this article. The authors have not responded to any correspondence from the editor or publisher about this retraction. References 1. Huang, S, Jin, A. ZIC2 promotes viability and invasion of human osteosarcoma cells by suppressing SHIP2 expression and activating PI3K AKT pathways. J Cell Biochem. 2018;119:2248u201357. https: doi.org 10.1002 jcb.26387 ,