Ras-PI3K pathway promotes osteosarcoma progression via regulating VRK1-mediated H2A phosphorylation at threonine 120
Authors: Xianlun Xu
Hao Yu
Journal: Artificial Cells Nanomedicine and Biotechnology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Osteosarcoma; Ras-PI3K pathway; VRK1; histone H2A.
Affiliations: Department of Traumatology, Jining No.1 People's Hospital, Jining, Shandong, China., Affiliated Jining No. 1 People's Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, China.

Abstract:  Background: Ras-PI3K pathway aberrant activation plays an important role in the occurrence and development of osteosarcoma. This study investigated the functions of Ras-PI3K pathway specific activation on histone H2A phosphorylation at threonine 120 (H2AT120ph) in osteosarcoma cells, along with the possible internal molecular mechanisms.Methods: Cell transfection was done to alter RasG12V/Y40C, H2AT120ph and vaccinia-related kinase 1 (VRK1) expression. Then, cell viability, proliferation, migration and cell cycle distribution were assessed, respectively. qRT-PCR was utilized to measure the VRK1 and Ras-PI3K pathway downstream genes (CYR61, IGFBP3, WNT16B, NT5E, GDF15 and CARD16) expression. Chromatin immunoprecipitation (ChIP) was conducted to evaluate the input levels of H2AT120ph and VRK1 in the promoter regions of Ras-PI3K pathway downstream genes.Results: Ras-PI3K specific activation promoted histone H2AT120ph. H2AT120ph participated in the oncogenic functions of Ras-PI3K pathway on osteosarcoma by modulating the transcription of Ras-PI3K-targeted genes. Moreover, VRK1 contributed to the Ras-PI3K specific activation-induced up-regulation of H2AT120ph and osteosarcoma progression. Ras-PI3K pathway-specific activation-induced up-regulation of H2AT120ph was achieved by up-regulation of VRK1.Conclusions: Ras-PI3K pathway activation promoted osteosarcoma progression might be via up-regulating VRK1-mediated H2AT120ph. We proposed that VRK1 and H2AT120ph could be the potential targets for osteosarcoma diagnosis and treatment.HighlightsH2AT120ph is specifically promoted by Ras-PI3K pathway activation.H2AT120ph joins in the oncogenic effects of Ras-PI3K pathway on osteosarcoma.H2AT120ph regulates the transcription of Ras-PI3K-targeted genes.VRK1 takes part in the regulatory function of Ras-PI3K pathway on H2AT120ph. 

Retracted: No

PubPeer comments:
 2021 retraction. https: www.frontiersin.org articles 10.3389 fimmu.2021.716458 full RETRACTION article Front. Immunol., 14 June 2021 | https: doi.org 10.3389 fimmu.2021.716458 Retraction: Corrigendum: Akt2 Regulates the Differentiation and Function of NKT17 Cells via FoxO-1-ICOS Axis Frontiers Editorial Office* A Retraction of the Correction Article Corrigendum: Akt2 Regulates the Differentiation and Function of NKT17 Cells via FoxO-1-ICOS Axis by Niu L, Xuan X, Wang J, Li L, Yang D, Jing Y, Westerberg LS and Liu C (2020). Front. Immunol. 11:589346. doi: 10.3389 fimmu.2020.589346 The journal and Chief Editors retract the 30 September 2020 article cited above. Following the publication of the article, image duplication concerns were identified in the published article, specifically in Figure 3J. The authors were unable to provide a satisfactory explanation for this occurrence despite issuing a Correction article. As a result, the data and conclusions of the article have been deemed unreliable. The Correction article is therefore being retracted. The authors concur with the retraction and sincerely regret any inconvenience this may have caused to the reviewers, editors and readers of Frontiers in Immunology. ,