RETRACTED ARTICLE: K-RasG12V/Y40C-PI3K/AKT pathway regulates H1.4S35ph through PKA to promote the occurrence and development of osteosarcoma cancer
Authors: Wanguo Liu
Hang Dong
Wenjun Wang
Jingzhe Zhang
Journal: Artificial Cells Nanomedicine and Biotechnology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: H1.4S35ph; MDM2; Osteosarcoma; PKA; RasG12V/Y40C-PI3K/AKT.
Affiliations: a Department of Orthopedics, China-Japan Union Hospital of Jilin University , Changchun , China.

Abstract:  Background: Osteosarcoma is prevalent in children and adolescents. H1.4 modification is involved in various types of cancers. Ras pathway is often activated in human cancers. Herein, we explored the effects of Ras pathway through H1.4S35ph. Methods: Osteosarcoma cancer cell line MG-63 was transfected with Ras gene with G12V and Y40C site mutation. The phosphorylation of H1.4S35 and AKT was detected by Western blot. Cell viability, cell colonies and migration were analyzed by MTT assay, soft-agar colony formation assay and Transwell assay, respectively. The expression of Ras pathway downstream factors and PKA was detected by qRT-PCR. The relationship between Ras and downstream factors was detected by ChIP. The cell cycle progression was measured by flow cytometry. Results: Transfection with RasG12V/Y40C decreased H1.4S35ph expression while switched on p-AKTSer473. RasG12V/Y40C increased cell viability, colony numbers and migration while H1.4S35E (H1.4S35ph overexpression) led to the opposite results. The regulation of RasG12V/Y40C and H1.4S35E on Ras downstream factors was contrary to each other. Results demonstrated a positive relationship between PKA with H1.4S35ph with RasG12V/Y40C down-regulated both. However, PKA and MDM2 revealed negative regulation with RasG12V/Y40C transfection up-regulated MDM2. Conclusion: RasG12V/Y40C-PI3K/AKT signal pathway decreased H1.4S35ph through down-regulation of PKA while up-regulation of MDM2 in MG-63 cells. Highlights H1.4S35ph is regulated by K-RasG12V/Y40-PI3K/AKT in MG-63 cells; Overexpression of H1.4S35ph regulates MG-63 cell growth; H1.4S35ph regulates Ras downstream factors; K-RasG12V/Y40C-PI3K/AKT activity induces PKA degradation to down-regulate H1.4S35ph; K-RasG12V/Y40C-PI3K/AKT activity involves in PKA degradation via MDM2. 

Retracted: Yes

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 , 
 Retracted [22nd May 2020] .  Since publication, the authors noticed that the data and figures in their article need to be modified. As these errors directly impact the reported results and conclusions the authors alerted the issue to the Editor and Publisher and all have agreed to retract the article to ensure correction of the scholarly record. ,