scholarly journals miR-217 regulates tumor growth and apoptosis by targeting the MAPK signaling pathway in colorectal cancer

2016 ◽  
Vol 12 (6) ◽  
pp. 4589-4597 ◽  
Author(s):  
Nan Zhang ◽  
Canrong Lu ◽  
Lin Chen
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway

scholarly journals Cholesterol Enhances Colorectal Cancer Progression via ROS Elevation and MAPK Signaling Pathway Activation

2017 ◽  
Vol 42 (2) ◽  
pp. 729-742 ◽  
Author(s):  
Caihua Wang ◽  
Peiwei Li ◽  
Junmei Xuan ◽  
Chunpeng Zhu ◽  
Jingjing Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Signaling Pathway ◽  
High Fat Diet ◽  
Ldl Receptor ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
High Fat

Background/Aims: Elevated serum cholesterol levels were linked to a higher risk of colorectal adenoma and colorectal cancer (CRC), while the effect of cholesterol on CRC metastasis has not been widely studied. Methods: CRC patients were enrolled to evaluate the association between low-density lipoprotein cholesterol (LDL) and CRC metastases, and LDL receptor (LDLR) level of the CRC tissue was assessed by immunohistochemistry. The effects of LDL on cell proliferation, migration and stemness were assessed in CRC cells in vitro, and the effects of high fat diet (HFD) on tumor growth and intestinal tumorigenicity were investigated in vivo. ROS assays, gene expression array analysis and western blot were used to explore the mechanisms of LDL in CRC progression. Results: The level of LDL was positively correlated with liver metastases, and a higher level of LDL receptor (LDLR) expression was associated with advanced N and M stages of CRC. In vitro, LDL promoted the migration and sphere formation of CRC cells and induced upregulated expression of “stemness” genes including Sox2, Oct4, Nanog and Bmi 1. High-fat diet (HFD) significantly enhanced tumor growth in vivo, and was associated with a shorter intestinal length in azoxymethane/dextran sodium sulfate (AOM/DSS)-treated mice. Furthermore, LDL significantly elevated reactive oxygen species (ROS) levels and Whole Human Genome Microarray found 87 differentially expressed genes between LDL-treated CRC cells and controls, which were largely clustered in the MAP kinase (MAPK) signaling pathway. Conclusions: LDL enhances intestinal inflammation and CRC progression via activation of ROS and signaling pathways including the MAPK pathway. Inflammation is strongly associated with cancer initiation, and the role of LDL in intestinal tumorigenicity should be further explored.

The potential role of regulatory microRNAs of RAS/MAPK signaling pathway in the pathogenesis of colorectal cancer

2019 ◽  
Vol 120 (12) ◽  
pp. 19245-19253 ◽  
Author(s):  
Atena Soleimani ◽  
Farzad Rahmani ◽  
Nikoo Saeedi ◽  
Rana Ghaffarian ◽  
Majid Khazaei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Potential Role ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway

scholarly journals TIMP-2 Regulates 5-Fu Resistance via the ERK/MAPK Signaling Pathway in Colorectal Cancer

2020 ◽  
Author(s):  
Guolin Zhang ◽  
Xin Luo ◽  
Jianbin Xu ◽  
Wei Zhang ◽  
Engeng Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Signaling Pathway ◽  
Resistance Mechanism ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Erk Mapk ◽  
Colorectal Cancer Patients ◽  
Autocrine Mechanism

Abstract Background: 5-Fluorouracil (5-Fu) is the first-line chemotherapeutic drug in the treatment of colorectal cancer. The efficiency of 5-Fu is limited by drug resistance in colorectal cancer patients. This study was aimed to define the functions of tissue inhibitor metalloproteinases 2 (TIMP-2) in the 5-Fu resistance to colorectal cancer and investigate its potential mechanism.Methods: Cytokine array, ELISA and RT-qPCR were performed to detect cytokine expression levels. Western blot and immunohistochemistry were used to show the differential expression of proteins. In addition, cell viability was detected by CCK-8.Results: We established that there is an up-regulation in the expression of the TIMP-2 in colorectal cancer patients. This up-regulation in TIMP-2 expression was evident in 5-Fu resistant colorectal cancer patients and resulted in a poor prognosis. Besides, in vivo, clinical studies and patient-derived xenograft (PDX) models confirmed that TIMP-2 was highly expressed in the 5-Fu-resistant colorectal cancer. We deduced an autocrine mechanism through which elevated TIMP-2 protein levels sustained colorectal cancer cell resistance to 5-Fu by constitutively activating the ERK/MAPK signaling pathway via an autocrine mechanism. The 5-Fu resistance could overcome by the inhibition of TIMP-2 by anti-TIMP-2 antibody or ERK/MAPK by U0126.Conclusion: Our findings identify a TIMP-2-ERK/MAPK mediated 5-Fu resistance mechanism in colorectal cancer. Moreover, we recommend the use of an ERK/MAPK signal pathway inhibitor or TIMP-2-mediated immunotherapy for 5-Fu resistant colorectal cancer.

scholarly journals STOML2 Interacts with PHB through Activating MAPK Signaling Pathway to Promote Colorectal Cancer Proliferation.

2020 ◽  
Author(s):  
Wenhui Ma ◽  
Yuehong Chen ◽  
Wenyi Li ◽  
Zhuoluo Xu ◽  
Zhigang Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Regulatory Mechanism ◽  
Biological Process ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Interacting Proteins ◽  
Yeast Two Hybrid ◽  
Cancer Proliferation ◽  
Two Hybrid

Abstract BackgroundOverexpression of STOML2 has been widely reported in a variety of cancer, yet few has detailed its function and regulatory mechanism. This study aims to reveal the clinicopathologic significance and oncologic function of STOML2 in colorectal cancer, explore its specific mechanism by means of yeast two-hybrid assay and bioinformatics.MethodsExpression level of STOML2 in normal colon and CRC tissue from biobank in Nanfang Hospital was detected by pathologic methods. The malignant proliferation of CRC induced by STOML2 was validated via gain-of-function and loss-of-function experiments, with novel techniques applied, such as organoid culture, orthotopic model and endoscopy monitoring. Yeast two-hybrid assay was conducted to screen interacting proteins of STOML2, followed by bioinformatics to predict biological process and signaling pathway of candidate proteins. Target protein with most functional similarity to STOML2 was validated with co-immunoprecipitation, and immunofluorescence were conducted to co-localize STOML2 and PHB. Pathway regulated by STOML2 was detected with immunoblotting, and subsequent experimental therapy was conducted with RAF inhibitor Sorafenib.ResultsSTOML2 was significantly overexpressed in colorectal cancer and its elevation was associated with unfavorable prognosis. Knockdown of STOML2 suppressed proliferation of colorectal cancer, thus attenuated subcutaneous and orthotopic tumor growth, while overexpressed STOML2 promoted proliferation in cell lines and organoids. A list of 13 interacting proteins was screened out by yeast two-hybrid assay. DTYMK and PHB were identified to be most similar to STOML2 according to bioinformatics in terms of biological process and signaling pathways; however, co-immunoprecipitation confirmed interaction between STOML2 and PHB, rather than DTYMK, despite its highest rank in previous analysis. Co-localization between STOML2 and PHB was confirmed in cell lines and tissue level. Furthermore, knockdown of STOML2 downregulated phosphorylation of RAF1, MEK1/2, ERK1/2 and ELK1 on the MAPK signaling pathway, indicating common pathway activated by STOML2 and PHB in colorectal cancer proliferation.ConclusionsThis study demonstrated that in colorectal cancer, STOML2 expression is elevated and interacts with PHB through activating MAPK signaling pathway, to promote proliferation both in vitro and in vivo. In addition, combination of screening assay and bioinformatics marks great significance in methodology to explore regulatory mechanism of protein of interest.

C8orf48 inhibits the tumorigenesis of colorectal cancer by regulating the MAPK signaling pathway

Life Sciences ◽  
2021 ◽  
Vol 266 ◽  
pp. 118872
Author(s):  
Lei Lei ◽  
Guoyan An ◽  
Ziqing Zhu ◽  
Shuzhen Liu ◽  
Yutong Fu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway

Melittin Suppresses VEGF-A-Induced Tumor Growth by Blocking VEGFR-2 and the COX-2-Mediated MAPK Signaling Pathway

2012 ◽  
Vol 75 (11) ◽  
pp. 1922-1929 ◽  
Author(s):  
Jeong-Eun Huh ◽  
Jung Won Kang ◽  
Dongwoo Nam ◽  
Yong-Hyeon Baek ◽  
Do-Young Choi ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Cox 2
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