scholarly journals Ribosomal protein S15A promotes malignant transformation and predicts poor outcome in colorectal cancer through misregulation of p53 signaling pathway

2016 ◽  
Vol 48 (4) ◽  
pp. 1628-1638 ◽  
Author(s):  
JINGWEN CHEN ◽  
YE WEI ◽  
QINGYANG FENG ◽  
LI REN ◽  
GUODONG HE ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Ribosomal Protein ◽  
Signaling Pathway ◽  
Malignant Transformation ◽  
Poor Outcome ◽  
P53 Signaling ◽  
P53 Signaling Pathway

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 iTRAQ-Based Proteomic Analysis of Ginsenoside F2on Human Gastric Carcinoma Cells SGC7901

2016 ◽  
Vol 2016 ◽  
pp. 1-21 ◽  
Author(s):  
Qian Mao ◽  
Pin-Hu Zhang ◽  
Jie Yang ◽  
Jin-Di Xu ◽  
Ming Kong ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Ribosomal Protein ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Beclin 1 ◽  
Human Gastric Cancer ◽  
P53 Signaling ◽  
Protein P53 ◽  
P53 Signaling Pathway

Ginsenoside F2(F2), a protopanaxdiol type of saponin, was reported to inhibit human gastric cancer cells SGC7901. To better understand the molecular mechanisms of F2, an iTRAQ-based proteomics approach was applied to define protein expression profiles in SGC7901 cells in response to lower dose (20 μM) and shorter duration (12 hour) of F2treatment, compared with previous study. 205 proteins were screened in terms of the change in their expression level which met our predefined criteria. Further bioinformatics and experiments demonstrated that F2treatment downregulated PRR5 and RPS15 and upregulated RPL26, which are implicated in ribosomal protein-p53 signaling pathway. F2also inhibited CISD2, Bcl-xl, and NLRX1, which are associated with autophagic pathway. Furthermore, it was demonstrated that F2treatment increased Atg5, Atg7, Atg10, and PUMA, the critical downstream effectors of ribosomal protein-p53 signaling pathway, and Beclin-1, UVRAG, and AMBRA-1, the important molecules in Bcl-xl/Beclin-1 pathway. The 6 differentially abundant proteins, PRR5, CISD2, Bcl-xl, NLRX1, RPS15, and RPL26, were confirmed by western blot. Taken together, ribosomal protein-p53 signaling pathway and Bcl-xl/Beclin-1 pathway might be the most significantly regulated biological process by F2treatment in SGC7901 cells, which provided valuable insights into the deep understanding of the molecular mechanisms of F2for gastric cancer treatment.

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

Chiaurinib Selectively Inhibits Colorectal Cancer with KRAS Wild-Type by Modulation of ROS through Activating the p53 Signaling Pathway

2020 ◽  
Author(s):  
Haofan Yin ◽  
Jineye Xie ◽  
Ping Jiang ◽  
Xi Jiang ◽  
Deyu Duan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Tunel Staining ◽  
Dependent Manner ◽  
Ros Production ◽  
Wild Type ◽  
P53 Signaling ◽  
P53 Signaling Pathway

Abstract Background: Colorectal cancer (CRC) is one of the top three most deadly cancers despite using chemotherapy based on oxaliplatin or irinotecan combined with targeted therapy. Chiaurinib has recently been identified to be a promising anticancer candidate with impressive efficacy and safety. However, the role and molecular mechanisms of Chiaurinib in the treatment of CRC remain to be elucidated.Methods: Cell proliferation and apoptosis were detected by CCK-8, EDU staining, Colony formation assay, TUNEL staining and flow cytometric analysis. ROS production was confirmed by Mito-SOX and DCF-DA fluorescence. RNA-Seq and GSEA analysis were used to explore the mechanisms of the effect of Chiaurinib in KRAS wild-type CRC cells.Results: Our study shows that Chiaurinib inhibits cell proliferation and induces apoptosis in KRAS wild-type CRC cells in a dose- and time-dependent manner, but not mutation ones. Meanwhile, Chiaurinib increases ROS production in KRAS wild-type CRC cells. Moreover, Chiaurinib selectively suppresses KRAS wild-type CRC cells growth in vivo. Mechanistically, Chiaurinib inhibits KRAS wild-type CRC cells by triggering ROS production via activating the p53 signaling pathway. Further, KRAS mutation CRC cells are resistant to Chiaurinib by increasing Nrf2 to stably elevate the basal antioxidant program and thereby lower intracellular ROS induced by Chiaurinib.Conclusions: Taken together, we reveal that Chiauranib induces p53 upregulation, resulting in ROS accumulation, thus inhibiting cell proliferation and inducing apoptosis in KRAS wild-type CRC cells. Our findings provide the rationale for further clinical evaluation of Chiaurinib as a therapeutic agent in treating KRAS wild-type CRC.

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