Ubiquitin specific peptidase 49 inhibits non‐small cell lung cancer cell growth by suppressing PI3K/AKT signaling

Shen, Wei; Yin, Jinnan; Xu, Ruijun; Xu, Danyan; Zheng, Shaojiang

doi:10.1002/kjm2.12073

Cited by 15 publications

(14 citation statements)

References 26 publications

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“…The PI3K/AKT/mTOR signaling has been reported to be hyperactivated in multiple kinds of cancers, including prostate cancer, leading to cell growth promotion and apoptosis repression [ 18 , 19 ]. PTEN (phosphatase and tensin homolog), located in human chromosome 10q23.3, is a negative regulator of PI3K/AKT/mTOR signaling [ 20 ]. Notably, PTEN has been identified as one of the most frequently deleted tumor suppressor genes in prostate cancer [ 21 , 22 ], which significantly contributes to the malignant progression of prostate cancer [ 23 – 25 ].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: IMP3 accelerates the progression of prostate cancer through inhibiting PTEN expression in a SMURF1-dependent way

Zhang

Wang

Liu

et al. 2020

J Exp Clin Cancer Res

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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.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: IMP3 accelerates the progression of prostate cancer through inhibiting PTEN expression in a SMURF1-dependent way

Zhang

Wang

Liu

et al. 2020

J Exp Clin Cancer Res

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“…Ubiquitination via E3 ligase RFP can downregulate PTEN phosphatase activity rather than altering its stability or localization [109]. As for the deubiquitination of PTEN, USP10, USP11, USP13, USP49, and OTUD3 catalyze removal of K48-linked ubiquitin chain on PTEN to enhance protein stability of PTEN and attenuate AKT signaling pathway [110][111][112][113][114]. USP7-induced deubiquitination of PTEN results in its nuclear exclusion rather than regulating its protein stability [115,116].…”

Section: Ubiquitination Of Ptenmentioning

confidence: 99%

The role of ubiquitination and deubiquitination in cancer metabolism

Sun¹,

Liu²,

Yang³

2020

Mol Cancer

253

178

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Metabolic reprogramming, including enhanced biosynthesis of macromolecules, altered energy metabolism, and maintenance of redox homeostasis, is considered a hallmark of cancer, sustaining cancer cell growth. Multiple signaling pathways, transcription factors and metabolic enzymes participate in the modulation of cancer metabolism and thus, metabolic reprogramming is a highly complex process. Recent studies have observed that ubiquitination and deubiquitination are involved in the regulation of metabolic reprogramming in cancer cells. As one of the most important type of post-translational modifications, ubiquitination is a multistep enzymatic process, involved in diverse cellular biological activities. Dysregulation of ubiquitination and deubiquitination contributes to various disease, including cancer. Here, we discuss the role of ubiquitination and deubiquitination in the regulation of cancer metabolism, which is aimed at highlighting the importance of this post-translational modification in metabolic reprogramming and supporting the development of new therapeutic approaches for cancer treatment.

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“…And the ubiquitination process of proteins consists of at least five important components, including ubiquitin (Ub), ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), ubiquitin ligase (E3) and deubiquitinating enzyme (DUB). [1][2][3] At present, it is estimated that there are 1-2 E1s, 60-100 E2s, 1000 E3s and nearly 100 DUBs in human cells. 4 Among them, the disorder of protein ubiquitination components is closely related to the occurrence and development of cancer.…”

Section: Introductionmentioning

confidence: 99%

<p>RING Finger Protein 38 Mediates LIM Domain Binding 1 Degradation and Regulates Cell Growth in Colorectal Cancer</p>

Huang

Yang

et al. 2020

OTT

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Background and Objectives: RING finger protein 38 (RNF38) has been reported to be involved in the tumorigenesis of several tumors, but its role in colorectal cancer (CRC) is still not investigated. In the present study, we aimed to investigate the effect of RNF38 in CRC cells. Materials and Methods: The public tumor databases GEPIA and Kaplan-Meier Plotter were used to analyze RNF38 expression and patients' overall survival in CRC. The qRT-PCR was carried out to assess the mRNA levels of RNF38 and LDB1. Western blot and co-immunoprecipitation were used to detect protein expression and ubiquitination. CCK-8 assay was performed to analyze CRC cell growth and viability. Results: RNF38 was found downregulated in CRC tumor tissues and cell lines, and CRC patients with high RNF38 expression had a longer overall survival than patients with low RNF38 expression. Our further investigations showed that RNF38 interacted with LDB1, and downregulated LDB1 expression by inducing its polyubiquitination. Moreover, overexpression of RNF38 inhibited CRC cell growth but enforced LDB1 could significantly antagonize RNF38-induced cell growth inhibition in CRC cells. Additionally, RNF38/LDB1 axis was involved in the drug sensitivity of 5-FU to CRC cells. Conclusion: Our studies suggested that RNF38 was functional in CRC cells, and downregulated CRC cell growth by inducing LDB1 polyubiquitination, which indicated that RNF38 could be as a novel target for CRC therapy.

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Ubiquitin specific peptidase 49 inhibits non‐small cell lung cancer cell growth by suppressing PI3K/AKT signaling

Cited by 15 publications

References 26 publications

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

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

The role of ubiquitination and deubiquitination in cancer metabolism

<p>RING Finger Protein 38 Mediates LIM Domain Binding 1 Degradation and Regulates Cell Growth in Colorectal Cancer</p>

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