Knockdown of PREX2a inhibits the malignant phenotype of glioma cells
Authors: Fuqiang Ruan
Shuai Wen
Long Chen
Liang Liu
Zhixiong Liu
Hao Wang
Jihui Zhang
Hengshan Luo
Yi Hu
Journal: Molecular Medicine Reports (2016)
Discipline: CLINICAL MEDICINE
Keywords: Glioma; PREX2a; PTEN; proliferation; apoptosis
Affiliations: Department of Neurosurgery, People's Hospital of Ningxiang County, Changsha, Hunan 410600, P.R. China., Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan 410078, P.R. China.

Abstract:  Glioma is the most common type of malignant brain tumor. Phosphatidylinositol‑3,4,5‑trisphosphate‑dependent Rac exchange factor 2a (PREX2a), which is a regulator of the small guanosine triphosphatase Rac, has previously been identified as an oncoprotein that inhibits phosphatase and tensin homolog deleted on chromosome 10 (PTEN) activity. However, the role of PREX2a in the regulation of the malignant phenotype of glioma has yet to be reported. The present study demonstrated that the mRNA and protein expression levels of PREX2a were significantly increased in glioma tissue, as compared with in normal brain tissue. Furthermore, the expression levels of PREX2a were positively correlated with tumor grade. PREX2a‑specific small interfering RNA‑mediated knockdown significantly inhibited proliferation and induced apoptosis of SWO‑38 glioma cells. Furthermore, inhibition of PREX2a expression significantly suppressed cell cycle progression in glioma cells, as detected by cell cycle arrest at G1 phase. In addition, knockdown of PREX2a inhibited the invasion of SWO‑38 glioma cells. The present study also investigated the molecular mechanisms underlying the effects of PREX2a knockdown, and demonstrated that phosphoinositide 3‑kinase signaling was significantly downregulated, which may be due to the upregulation of PTEN activity. In conclusion, the present study is the first, to the best of our knowledge, to suggest that knockdown of PREX2a may effectively inhibit the malignant phenotype of glioma in vitro; therefore, PREX2a may be considered a potential molecular target for the treatment of glioma. 

Retracted: Yes

PubPeer comments:
 Fig 4A.  Cell invasion assay was performed in SWO-38 cells transfected with phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2a (PREX2a) small interfering (si)RNA or non-specific negative control siRNA (NC). Control group represents untransfected SWO-38 cells . ![file] For comparison: *[above]* Fig 5 from [Peng et al (2013)] .  The invasion of U87 and CHG-5 cells after siRNA-mediated RACK1 downregulation . *[below]* Fig 4C from [Jiang et al (2016)] .  A Transwell assay was performed to examine the cell migration of GC7901 cells transfected with miR-27b inhibitor or pcDNA3.1-SPRY2 plasmids . Unexpected similarities. ![file] , 
 Fig 2D.  apoptosis assay . ![] Figs 1C, 4D from [Zhao et al (2015)] .  Overexpression of miR-148a promoted paclitaxel-induced cell apoptosis, whereas inhibition of miR-148a suppressed paclitaxel-induced cell apoptosis, compared with the control group ;  Overexpression of PDIA3 inhibited paclitaxel-induced cell apoptosis, whereas inhibition of PDIA3 promoted paclitaxel-induced cell apoptosis, compared with the control . ![] , 
 Fig 3.  Cell cycle distribution was analyzed in SWO-38 glioma cells transfected with phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2a (PREX2a) small interfering (si)RNA or non-specific negative control siRNA (NC). Control group represents untransfected SWO-38 cells. ![file] Panels match Fig 4A of [Liu et al (2014)] .  miR-22 inhibited E2-induced cell cycle progression in RL95-2 and Ishikawa cells. (A) Cell cycle assay was performed to investigate the effect of miR-22 on E2-induced cell cycle progression in RL95-2 and Ishikawa cells. ![file] , 
 Retracted [1 June 2021] . -------------------------------------------- Following the publication of this paper, it was drawn to the Editorsu2019 attention by a concerned reader that cell invasion assay data in the article (featured in Fig. 4A) were strikingly similar to data appearing in different form in another article by different authors at different research institutions, which had already been published elsewhere at the time of the present articleu2019s submission. Furthermore, flow cytometric data featured in Fig. 2D were strikingly similar to those in another previously published paper, and cell cyle data included in Fig. 3 had apparently previously published elsewhere. Owing to the fact that the contentious data in the above article had already appeared in different form in other articles prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors also expressed their intention to retract the paper on the grounds that the corresponding author and several of the authors failed to confirm the approval of the final version of the manuscript. The Editor apologizes to the readership for any inconvenience caused. -------------------------------------------- Background [here] . ,