Silencing SUMO2 promotes protection against degradation and apoptosis of nucleus pulposus cells through p53 signaling pathway in intervertebral disc degeneration
Authors: Ji-Shou Lu
Liu-Zhong Jin
Jian-Wen Gao
Journal: Bioscience reports (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Intervertebral disc degeneration; Nucleus pulposus cells; Proliferation; SUMO2 gene silencing; p53 signaling pathway.
Affiliations: Department of Spine Surgery, Jining No. 1 People's Hospital, Jining 272000, P.R. China., Department of Spine Surgery, Jining No. 1 People's Hospital, Jining 272000, P.R. China .

Abstract:  Objective: Intervertebral disc degeneration (IDD), as a common cause of back pain, is related to the promotion of cellular senescence and reduction in proliferation. Based on recent studies, small ubiquitin-related modifier (SUMO) proteins have been implicated in various biological functions. Therefore, in the present study, we investigated the effects of SUMO2 on proliferation and senescence of nucleus pulposus cells (NPCs) via mediation of p53 signaling pathway in rat models of IDD. Methods: After the establishment of rat models of IDD for the measurement of positive expression of SUMO2/3 protein, the mRNA and protein levels of SUMO2, molecular phenotype [matrix metalloproteinase-2 (MMP-2) and hypoxia-inducible factor-1α (HIF-1α)] and p53 signaling pathway-related genes [p21, murine double minute-2 (MDM2), growth arrest and DNA-damage-inducible protein 45 α (GADD45α), cyclin-dependent kinase 2/4 (CDK2/4), and CyclinB1] were determined, followed by the detection of cell proliferation, cell cycle, apoptosis, and cell senescence. Results: The rat models of IDD were successfully constructed. The results obtained showed that there was a higher positive expression of SUMO2/3 protein in IDD rats. Moreover, the silencing of the SUMO2 gene decreases the levels of SUMO2, p53, p21, MDM2, GADD45α, MMP-2, and HIF-1α expressions and p53 phosphorylation level while it increases the levels of CDK2/4 and CyclinB1 expressions. In addition, SUMO2 gene silencing enhances proliferation and suppresses apoptosis and cell senescence of NPCs. Conclusion: In conclusion, SUMO2 gene silencing promotes proliferation, and inhibits the apoptosis and senescence of NPCs in rats with IDD through the down-regulation of the p53 signaling pathway. Thus, SUMO2 is a potential target in the treatment of IDD. 

Retracted: No

PubPeer comments:
 Fig 8A:  Flow cytometry analysis of PI staining shows that SUMO2 gene silencing promotes cell cycle entry of NPCs Notes: (A) Cell cycle entry of NPCs in the sham, model, NC, and shRNA groups . ![file] Fig 4A from [Wang et al (2018)] .  Cell cycles of SW480 and HCT116 cells among four groups at 48 h after transfection by flow cytometry with PI staining Notes: A-B, cell cycle of SW480 cell among four groups . ![file] Areas of similarity marked. , 
 Expression of Concern, [28 August 2020] .  The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates. , 
 #2 The editorial investigation will soon enter its second year. Without wanting to delay the editors further, I invite them to extend their inquiry to include Fig 9A, where the panels largely consist of vertically-elongated double-pixel data-points, but with a minority of single-pixel data-points. ![file] Here, comparing the sh-RNA panel with the Normal Control panel of Fig 9C from [Cai et al (2018)] . Not identical but an uncanny resemblance. ![file] ------------------------------------------- Also, Fig 6C. ![file] Compare, for instance, [this montage] : ![] Not to forget Fig 6A C of [Wang et al (2018)] . ![] They seem to be sampling one small, familiar corner of  shape space . ![] , 
 Retracted [6 October 2021] . ------------------------------- This Retraction follows an Expression of Concern relating to this article previously published by Portland Press. This article is being retracted from* Bioscience Reports* at the request of the Editor-in-Chief and the Editorial Board following receipt of a notification from a reader, alerting the Editorial Board to concerns in Figure 8A, which in part overlap with those published in Journal of Cellular Biochemistry (10.1002 jcb.26330). In addition, the Editorial Office has identified regions of duplication in Electron microscope IDD panel of Figure 1. The authors have been contacted in regards to the Retraction, and have not responded to the Journal s queries and the concerns raised. Given the extent of the issues raised, the Editorial Board stand by the decision to retract the article. , 
 - *[left]* Figs 2 and 6 from  Effect and mechanism of inhibition of PI3K Akt mTOR signal pathway on chronic neuropathic pain and spinal microglia in a rat model of chronic constriction injury ([Guo et al 2017] ). - *[right]* **Fig 2A** - flipped through 180 deg for ease of comparison. How to explain the duplications and overlaps? .![file] ,