RETRACTED ARTICLE: IMP3 accelerates the progression of prostate cancer through inhibiting PTEN expression in a SMURF1-dependent way

Abstract

Background Insulin-like growth factor 2 (IGF2) messenger RNA binding protein 3 (IMP3) has been testified to be overexpressed in prostate cancer and strongly related to patients’ poor prognosis. However, the functions of IMP3 and the underlying mechanisms in prostate cancer still remain unknown. Therefore, the current study was carried out to reveal the role and molecular mechanism of IMP3 in prostate cancer progression. Methods The expression levels of IMP3 in prostate cancer tissues and cells were detected by immunohistochemistry (IHC), western blotting and RT-PCR. CCK-8, clone formation, flow cytometry and in vivo tumor formation assays were used to determine cell growth, clone formation apoptosis and tumorigenesis, respectively. The effect of IMP3 on the expression levels of the key proteins in PI3K/AKT/mTOR signaling pathway, including PIP2, PIP3, p-AKT, AKT, p-mTOR, mTOR, PTEN and BAD activation of was determined by western blotting. IP (Immunoprecipitation) assay was used to evaluate the effects of IMP3 and SMURF1 (SMAD specific E3 ubiquitin protein ligase 1) on the ubiquitination of PTEN protein. Results IMP3 expression level was significantly increased in prostate cancer tissues and cell lines (LNCap, PC3 and DU145) as compared with the paracancerous normal tissues and cells (RWPE-1), respectively. High expression of IMP3 apparently promoted cell viability, tumorigenesis and inhibited cell apoptosis in prostate cancer LNCap, DU145 and PC3 cell lines. In mechanism, IMP3 upregulation significantly increased the phosphorylation levels of AKT and mTOR, and elevated PIP3 expression level, while induced significant reductions in the expression levels of BAD, PTEN and PIP2. And, IMP3 overexpression increased SMURF1 expression, which facilitated PTEN ubiquitination. In addition, SMURF1 overexpression enhanced prostate cancer cell viability and inhibited cell apoptosis. Silence of SMURF1 rescued the enhancements in cell proliferation and tumorigenesis and the inhibition in cell apoptosis rates induced by IMP3 in prostate cancer DU145 and LNCap cells. Conclusion This study reveals that IMP3 is overdressed in prostate cancer, which accelerates the progression of prostate cancer through activating PI3K/AKT/mTOR signaling pathway via increasing SMURF1-mediated PTEN ubiquitination.

Identification of MicroRNAs as Viable Aggressiveness Biomarkers for Prostate Cancer

“…There are also some reports in PC. Furthermore, the role of IGF2 messenger RNA binding protein 3 (IMP3) produces an acceleration in PC progression through activating PI3K/AKT/mTOR signaling pathway via increasing SMURF1-mediated PTEN ubiquitination [77]. All these data reinforce our results about the promising use of miR-93-5p as PC biomarkers.…”

Post-Translational Modifications That Drive Prostate Cancer Progression

“…Comprised of a catalytic C-terminal HECT domain and N-terminal C2 domain and WW domains responsible for cellular localization and substrate recognition IRS-2 [249]; AR [250]; ErbB3 levels and signaling [251] IGF signaling and mitogenic activity [249]; cancer cell proliferation in vitro and in vivo; sensitization of cancer cells for growth inhibition by an anti-ErbB3 antibody [251] SMURF1 SMAD specific E3 ubiquitin protein ligase 1 PTEN [252] PCa progression [252]; invasion [253] WWP1 WW domain-containing E3 ubiquitin protein ligase-1 TGFβ [254]; p63 [255]; KLF5 [256] Migration and invasion [257]; 22Rv1 cells colony formation; PC-3 cells proliferation and TGFβ-mediated growth inhibition [254]; apoptosis [255] WWP2…”

Comprehensive analysis to identify DLEU2L/TAOK1 axis as a prognostic biomarker in hepatocellular carcinoma

“…Phosphatase and tensin homolog (PTEN) is a very commonly mutated tumor suppressor gene in human cancers, including HCC. 26 , 27 , 28 , 29 Accumulating evidence has shed light on PTEN activity, which can be regulated by mutations, epigenetic silencing, abnormal protein, transcriptional inhibition, localization, and posttranslational modification. 30 , 31 , 32 At the same time, some data have indicated that decreased PTEN expression is a common event in HCC and is associated with disease stage, tumor grade and size, and increased expression of tumor markers.…”