Knockdown of PREX2a inhibits the malignant phenotype of osteosarcoma cells
Authors: Yihe Hu
Zixun Dai
Jie Xie
Pengfei Lei
Journal: Molecular Medicine Reports (2016)
Discipline: CLINICAL MEDICINE
Keywords: PREX2a; osteosarcoma; PTEN; PI3K signaling; cell proliferation
Affiliations: Department of Orthopedics, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.

Abstract:  Phosphatidylinositol‑3,4,5‑trisphosphate‑dependent Rac exchange factor 2a (PREX2a), which is a regulator of the small guanosine triphosphatase Rac, has recently been reported to have an oncogenic role via the suppression of phosphatase and tensin homolog deleted on chromosome ten (PTEN) activity, and the subsequent activation of phosphoinositide 3‑kinase (PI3K) signaling. However, the detailed role of PREX2a in osteosarcoma (OS) remains unclear. Reverse transcription quantitative polymerase chain reaction and western blotting was used to detect mRNA and protein levels. MTT assay was performed to examine cell proliferation and a Transwell assay and wound healing assay were conducted to examine cell invasion and migration. The present study demonstrated that PREX2a was markedly upregulated in OS cell lines, as compared with in normal osteoblast hFOB1.19 cells. In addition, knockdown of PREX2a expression significantly inhibited OS cell proliferation, whereas overexpression of PREX2a markedly promoted OS cell proliferation. Inhibition of PREX2a also markedly suppressed the invasion and migration of OS cells, at least partly by suppressing the protein expression of matrix metalloproteinase (MMP)2 and MMP9. Conversely, upregulation of PREX2a enhanced OS cell invasion and migration. In addition, PI3K signaling activity was significantly reduced following knockdown of PREX2a, and this was accompanied by an upregulation of PTEN activity. The results of the present study suggested that PREX2a may act as an oncogene in OS via the inhibition of PTEN activity and activation of PI3K signaling. 

Retracted: Yes

PubPeer comments:
 Fig 4A B.  Cell invasion assay was performed (A) in MG63 cells transfected with PREX2a siRNA or nonu2011specific siRNA (NC); and (B) in MG63 cells transfected with pcDNA3.1u2011PREX2a plasmid or blank pcDNA3.1 vector . ![file] For comparison, Figs 3B and 4 from [Deng et al (2015)] .  Transwell assay was used to determine the migratory capacity of ICC-9810 cells transfected with miR-101 mimics, VEGF-C siRNA, or co-transfected with miR-101 mimics and VEGF-C plasmid ;  Transwell assay was performed to determine the invasive capacity of ICC-9810 intrahepatic cholangiocarcinoma cells transfected with microRNA (miR)-101 mimics, vascular endothelial growth factor (VEGF)-C small interfering (si)RNA, or co-transfected with miR-101 mimics and VEGF-C plasmid. ![file] , 
 Retracted [7 February 2022] .  Following the publication of this paper, it was drawn to the Editorsu2019 attention by a concerned reader that the Transwell cell migration assay data shown in Fig. 4A and B were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to *Molecular Medicine Reports*, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. ,