K-Ras-ERK1/2 accelerates lung cancer cell development via mediating H3 through the MDM2-GCN5-SIRT7 axis
Authors: Xiufeng Li
Yi Sun
Yubing Wu
Shizhen Hou
Ziming Cheng
Bing Liu
Journal: Pharmaceutical biology (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: ERK1/2 downstream factors; K-Ras; NCI-H2126 cells; cell proliferation; migration.
Affiliations: Department of Thoracic Surgery, Linyi Central Hospital, Linyi, China

Abstract:  Context: H3K18ac is linked to gene expression and DNA damage. Nevertheless, whether H3K18ac participates in regulating Ras-ERK1/2-affected lung cancer cell phenotypes remains unclear. Objective: We explored the effects of H3K18ac on Ras-ERK1/2-affected lung cancer cell phenotypes. Material and methods: NCI-H2126 cells were transfected with, pEGFP-K-RasWT and pEGFP-K-RasG12V/T35S plasmids for 48 h, and transfection with pEGFP-N1 served as a blank control. Then H3K18ac and AKT and ERK1/2 pathways-associated factors were examined. Different amounts of the H3K18Q (0.5, 1, and 2 μg) plasmids and RasG12V/T35S were co-transfected into NCI-H2126 cells, cell viability, cell colonies and migration were analyzed for exploring the biological functions of H3K18ac in NCI-H2126 cells. The ERK1/2 pathway downstream factors were detected by RT-PCR and ChIP assays. The regulatory functions of SIRT7, GCN5 and MDM2 in Ras-ERK1/2-regulated H3K18ac expression were finally uncovered. Results: RasG12V/T35S transfection decreased the expression of H3K18ac about 2.5 times compared with the pEGFP-N1 transfection group, and activated ERK1/2 and AKT pathways. Moreover, H3K18ac reduced cell viability, colonies, migration, and altered ERK1/2 downstream transcription in NCI-H2126 cells. Additionally, SIRT7 knockdown increased H3K18ac expression and repressed cell viability, migration and the percentage of cells in S phase by about 50% compared to the control group, as well as changed ERK1/2 downstream factor expression. Besides, Ras-ERK1/2 decreased H3K18ac was linked to MDM2-regulated GCN5 degradation. Conclusion: These observations disclosed that Ras-ERK1/2 promoted the development of lung cancer via decreasing H3K18ac through MDM2-mediated GCN5 degradation. These findings might provide a new therapeutic strategy for lung cancer. 

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 ,