scholarly journals c-Jun Transcriptional Regulates NPRL2 to Promote the Proliferation Activity of Prostate Cancer Cells via AKT/MDM2/p53 Signaling Pathway

2020 ◽  
Author(s):  
Daixing Hu ◽  
Li Jiang ◽  
Shengjun Luo ◽  
Xin Zhao ◽  
Guozhi Zhao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Transcription Factor ◽  
Signaling Pathway ◽  
The Cancer Genome Atlas ◽  
Expression Level ◽  
Luciferase Reporter ◽  
P53 Signaling ◽  
Factor C ◽  
Cancer Tissues ◽  
P53 Signaling Pathway

Abstract BackgroundHigh NPRL2 (Nitrogen permease regulator-like 2) expression is a prognostic marker for poor clinical outcomes in prostate cancer (PCa). However, the regulatory mechanisms of NPRL2 in PCa remain unknown.MethodsThe expression level of NPRL2 in prostate cancer tissues were verified through The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The effect of NPRL2 gene in promoting the proliferation of prostate cancer was determined by CCK8 and clone formation assays. The apoptosis rate and cell cycle analysis were tested by flow cytometry. Luciferase reporter gene and ChIP were used to verify the binding relationship between transcription factor c-Jun and the NPRL2 5’ region. The effect of NPRL2 and the MK2206 on the AKT/MDM2/p53 signaling pathway was verified by western blotting.ResultsNPRL2 expression level was significantly increased in prostate cancer tissues than normal tissues base on TCGA and GEO database. We investigated that transcription factor c-Jun can bind to the NPRL2 promoter and regulated NPRL2 transcription directly. Then, we revealed that NPRL2 significantly promotes proliferation and reduces apoptosis in PCa cells. Further mechanistic investigations revealed that NPRL2 mediated proliferation promotion effect is associated with the AKT/MDM2/p53 pathway's participation. Besides, CDK2 might serve as an intermediate effector for NPRL2 to regulate the AKT pathway. ConclusionTaken together, our study identified that c-Jun contributes to transcriptional control of NPRL2 and NPRL2 can promote prostate cancer proliferation by activating AKT/MDM2/p53 signaling.

scholarly journals Fra-1 is upregulated in lung cancer tissues and inhibits the apoptosis of lung cancer cells by the P53 signaling pathway

2015 ◽  
Vol 35 (1) ◽  
pp. 447-453 ◽  
Author(s):  
GUANGWEI ZHONG ◽  
XI CHEN ◽  
XIA FANG ◽  
DONGSHENG WANG ◽  
MINGXUAN XIE ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Lung Cancer Cells ◽  
P53 Signaling ◽  
Cancer Tissues ◽  
P53 Signaling Pathway

scholarly journals IMP3 accelerates the progression of prostate cancer through inhibiting PTEN expression in a SMURF1-dependent way

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Xiang Zhang ◽  
Dawei Wang ◽  
Boke Liu ◽  
Xingwei Jin ◽  
Xianjin Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Western Blotting ◽  
Cell Apoptosis ◽  
Expression Level ◽  
Mtor Signaling Pathway ◽  
Expression Levels ◽  
Cancer Tissues

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.

The Novel CircSLC6A6/miR-1265/C2CD4A Axis Promotes Colorectal Cancer Growth by Suppressing P53 Signaling Pathway

2021 ◽  
Author(s):  
Zeyin Rong ◽  
Zai Luo ◽  
Zhongmao Fu ◽  
Pengshan Zhang ◽  
Tengfei Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Western Blotting ◽  
Cdna Array ◽  
Luciferase Reporter ◽  
Regulation Mechanism ◽  
P53 Signaling ◽  
Rna Immunoprecipitation ◽  
Fresh Frozen ◽  
P53 Signaling Pathway

Abstract Background: Colorectal cancer (CRC) ranks as the third most frequently diagnosed cancer and is a leading cause of cancer-related deaths. Therefore, further researches were required to identify novel and more effective diagnoses and to identify molecular targets in treatment of CRC.Methods: CRC fresh frozen tissues and cell lines were used to detect C2CD4A expression by qRT-PCR and western blotting. The biological functions of C2CD4A were performed in vitro and in vivo. Western blotting, cDNA array, IP-MS, Co-IP, and Ubiquitination assay were used to analyze the interaction between C2CD4A and p53. Bioinformatics analysis, FISH, RNA sequencing, luciferase reporter assay, RNA immunoprecipitation, RNA pull-down and rescue experiments, were deployed to detect upstream regulation mechanism of C2CD4A.Results: C2CD4A was aberrantly upregulated in CRC tissues compared with adjacent normal colorectal tissues. C2CD4A knockdown significantly promoted cell apoptosis and with inhibited proliferation in vitro, and tumorigenicity in vivo, whereas C2CD4A overexpression had displayed an opposite effect. Moreover, circSLC6A6 was upregulated and positively associated with C2CD4A expression in CRC tissues. C2CD4A was positively regulated by circSLC6A6 via sponging miR-1265. Fundamentally, C2CD4A inhibited P53 signaling pathway through interacting with P53 and increasing its ubiquitination and degradation.Conclusion: Our results identified that circSLC6A6/miR-1265/C2CD4A axis, which was involved in CRC via the P53 signaling pathway, could be as a therapeutic target for CRC.

scholarly journals Fra-1 is upregulated in gastric cancer tissues and affects the PI3K/Akt and p53 signaling pathway in gastric cancer

2015 ◽  
Vol 47 (5) ◽  
pp. 1725-1734 ◽  
Author(s):  
JUNYU HE ◽  
GUANGCHAO ZHU ◽  
LU GAO ◽  
PAN CHEN ◽  
YUEHUA LONG ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
P53 Signaling ◽  
Cancer Tissues ◽  
P53 Signaling Pathway

scholarly journals The novel circSLC6A6/miR-1265/C2CD4A axis promotes colorectal cancer growth by suppressing p53 signaling pathway

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Zeyin Rong ◽  
Zai Luo ◽  
Zhongmao Fu ◽  
Pengshan Zhang ◽  
Tengfei Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Western Blot ◽  
Signaling Pathway ◽  
Cdna Array ◽  
Luciferase Reporter ◽  
Regulation Mechanism ◽  
The Novel ◽  
P53 Signaling ◽  
Rna Immunoprecipitation ◽  
P53 Signaling Pathway

Abstract Background Colorectal cancer (CRC) is one of the most frequent malignancy and a leading cause of cancer-related deaths. Therefore, further researches are required to identify novel and more effective diagnoses and to identify molecular targets in treatment of CRC. Methods C2CD4A expression in CRC tissues and cell lines was detected by qRT-PCR and western blot. The biological functions of C2CD4A were performed both in vitro and in vivo. Western blot, cDNA array, IP-MS, Co-immunoprecipitation assay, and Ubiquitination assay were used to analyze the interaction between C2CD4A and p53. Bioinformatics analysis, FISH, RNA sequencing, luciferase reporter assay, RNA immunoprecipitation, RNA pull-down and rescue experiments, were deployed to detect upstream regulation mechanism of C2CD4A. Results C2CD4A was elevated in CRC tissues compared with adjacent normal colorectal tissues. C2CD4A knockdown significantly promoted cell apoptosis and with inhibited proliferation in vitro, and tumorigenicity in vivo, whereas C2CD4A overexpression led to opposite effects. Moreover, circSLC6A6 was upregulated and shown to positively regulate C2CD4A expression via sponging miR-1265. Fundamentally, C2CD4A inhibited p53 signaling pathway through interacting with p53 and increasing its ubiquitination and degradation. Conclusion Our results identified that circSLC6A6/miR-1265/C2CD4A axis, which was involved in CRC via the p53 signaling pathway, may serve as a therapeutic target for CRC.

The Molecular Docking of Flavonoids Isolated from Daucus carota as a Dual Inhibitor of MDM2 and MDMX

2020 ◽  
Vol 15 (2) ◽  
pp. 154-164 ◽  
Author(s):  
Ijaz Muhammad ◽  
Noor Rahman ◽  
Gul E. Nayab ◽  
Sadaf Niaz ◽  
Mohibullah Shah ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cancer Therapy ◽  
Natural Product ◽  
Signaling Pathway ◽  
In Silico ◽  
P53 Protein ◽  
Dual Inhibitor ◽  
P53 Signaling ◽  
In Silico Studies ◽  
P53 Signaling Pathway

Background: Cancer is characterized by overexpression of p53 associated proteins, which down-regulate P53 signaling pathway. In cancer therapy, p53 activity can be restored by inhibiting the interaction of MDMX (2N0W) and MDM2 (4JGR) proteins with P53 protein. Objective: In the current, study in silico approaches were adapted to use a natural product as a source of cancer therapy. Methods: In the current study in silico approaches were adapted to use a natural product as a source of cancer therapy. For in silico studies, Chemdraw and Molecular Operating Environment were used for structure drawing and molecular docking, respectively. Flavonoids isolated from D. carota were docked with cancerous proteins. Result: Based on the docking score analysis, we found that compound 7 was the potent inhibitor of both cancerous proteins and can be used as a potent molecule for inhibition of 2N0W and 4JGR interaction with p53. Conclusion: Thus the compound 7 can be used for the revival of p53 signaling pathway function however, intensive in vitro and in vivo experiments are required to prove the in silico analysis.

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