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 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.

scholarly journals β-catenin/LEF-1 Transcription Complex is Responsible for the Transcriptional Activation of LINC01278

2020 ◽  
Author(s):  
Shaojian Lin ◽  
Weiwei Zhang ◽  
Ziwen Shi ◽  
Langping Tan ◽  
Yue Zhu ◽  
...  
Keyword(s):  
Western Blot ◽  
Signaling Pathway ◽  
Transcriptional Activation ◽  
Feedback Regulation ◽  
Luciferase Reporter ◽  
Regulation Mechanism ◽  
Putative Promoter ◽  
Negative Feedback Regulation ◽  
Pathway Activation ◽  
Rna Immunoprecipitation

Abstract Background: Our previous study shows that LINC01278 inhibits the development of papillary thyroid carcinoma (PTC) by regulating miR-376c-3p/DNM3 axis. However, the regulation mechanism of LINC01278 expression in PTC cells is still unclear. Methods: The luciferase reporter and ChIP assays were used to confirme the binding of LEF-1 to the putative promoter site of LINC01278. The RNA immunoprecipitation was used the enrichment of LINC01278 in β-catenin protein. Western blot was used to detected the expression of target proteins. Results: Firstly, the online PROMO algorithm determined a putative LEF-1 binding site on LINC01278 promoter. Then, the luciferase reporter and ChIP assays confirmed the binding of LEF-1 to the putative promoter site of LINC01278. Furthermore, the overexpression of β-catenin increased the binding of LEF-1 to the LINC01278 promoter, and the knockdown or overexpression of LEF-1 or β-catenin can affect the expression level of LINC01278. In addition, RNA immunoprecipitation showed that LINC01278 was enriched in β-catenin protein. RNA pulldown and western blot also confirmed that LINC01278 precipitated β-catenin in TPC-1 and BCPAP cells. Furthermore, the knockdown or overexpression of LINC01278 significantly affected the expression of β-catenin and targets of Wnt/β-catenin signaling pathway (CCND2, CyclinD1, MYC, and SOX4). Conclusion: In summary, we found the transcriptional activation of LINC01278 by the β-catenin/LEF-1 transcription factor, and the negative feedback regulation of LINC01278 on Wnt/β-catenin signaling pathway activation.

scholarly journals Genetic variants in p53 signaling pathway genes predict chemotherapy efficacy in colorectal cancer

2019 ◽  
Vol 8 (7) ◽  
pp. 3428-3436 ◽  
Author(s):  
Ke Zhang ◽  
Yixuan Meng ◽  
Xiangming Cao ◽  
Ye Xu ◽  
Mulong Du ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Genetic Variants ◽  
P53 Signaling ◽  
Chemotherapy Efficacy ◽  
P53 Signaling Pathway

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.

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