scholarly journals A comprehensive investigation of colorectal cancer progression, from the early to late-stage, a systems biology approach

2020 ◽  
Author(s):  
Mohammad Ghorbani ◽  
Yazdan Asgari
Keyword(s):  
Colorectal Cancer ◽  
Wnt Signaling ◽  
Cancer Progression ◽  
Late Stage ◽  
Early Stage ◽  
Differentially Expressed Gene ◽  
Stage 4 ◽  
Colorectal Cancer Progression ◽  
Stage 1 ◽  
Canonical Wnt

AbstractColorectal cancer is a widespread malignancy with a concerning mortality rate. It could be curable at the first stages, but the progress of the disease and reaching to the stage-4 could make shift the treatments from curative to palliative. In this stage, the survival rate is meager, and therapy options are limited. The question is, what are the hallmarks of this stage and what genes are involved? What mechanism and pathways could drive such a malign shift from stage-1 to stage-4? In this study, first we identified the core modules for both the stage-1 and stage-4 which four of them have a significant role in stage-1 and two of them have a role in stage-4. Then we investigated the gene ontology and hallmarks analysis for each stage. According to the results, the immune-related process, especially interferon-gamma, impacts stage-1 in colorectal cancer. Concerning stage-4, extracellular matrix ontologies, and metastatic hallmarks are in charge. At last, we performed a differentially expressed gene analysis of stage-4 vs. stage-1 and analyzed their pathways which reasonably undergone a hypo/hyperactivity or being abnormally regulated through the cancer progression. We found that lncRNA in canonical WNT signaling and colon cancer has the most significant pathways, followed by WNT signaling, which means that these pathways may be the driver for the development from early-stage to late-stage. Of these lncRNAs, we had two upregulated kind, H19, and HOTAIR, which both can be involved and mediate metastasis and invasion in colorectal cancer.

scholarly journals CD151 promotes Colorectal Cancer progression by a crosstalk involving CEACAM6, LGR5 and Wnt signaling via TGFβ1

2021 ◽  
Vol 17 (3) ◽  
pp. 848-860
Author(s):  
Tao Yang ◽  
Huibing Wang ◽  
Meng Li ◽  
Linqi Yang ◽  
Yu Han ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Wnt Signaling ◽  
Cancer Progression ◽  
Colorectal Cancer Progression

scholarly journals MiR-532-3p suppresses colorectal cancer progression by disrupting the ETS1/TGM2 axis-mediated Wnt/β-catenin signaling

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Chuncai Gu ◽  
Jianqun Cai ◽  
Zhijun Xu ◽  
Shiming Zhou ◽  
Liangying Ye ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Molecular Therapy ◽  
Potential Candidate ◽  
Mesenchymal Transition ◽  
Plasma Microrna ◽  
Colorectal Cancer Progression ◽  
And Function ◽  
Canonical Wnt

Abstract The expression panel of plasma microRNA defined miR-532-3p as a valuable biomarker for colorectal adenoma (CRA). However, its expression pattern and function in colorectal cancer (CRC) have remained unclear. The present study investigated the expression levels of miR-532-3p and found that it was in situ downregulated both in CRA and CRC. Moreover, it functioned as a sensitizer for chemotherapy in CRC by inducing cell cycle arrest and early apoptosis via its activating effects on p53 and apoptotic signaling pathways. In addition, miR-532-3p was found to restrain cell growth, metastasis, and epithelial–mesenchymal transition (EMT) phenotype of CRC. A study on the mechanism behind these effects revealed that miR-532-3p directly binds to 3′UTR regions of ETS1 and TGM2, ultimately repressing the canonical Wnt/β-catenin signaling. Further investigation showed that TGM2 was transcriptionally regulated by ETS1 and ETS1/TGM2 axis served as a vital functional target of miR-532-3p in suppressing CRC progression. To conclude, miR-532-3p mimics could act as potential candidate for molecular therapy in CRC through inactivation of the canonical Wnt/β-catenin signaling and enhancement of chemosensitivity.

scholarly journals KRAS Mutation-Responsive miR-139-5p inhibits Colorectal Cancer Progression and is repressed by Wnt Signaling

Theranostics ◽  
2020 ◽  
Vol 10 (16) ◽  
pp. 7335-7350 ◽  
Author(s):  
Feng Du ◽  
Tianyu Cao ◽  
Huahong Xie ◽  
Ting Li ◽  
Lina Sun ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Wnt Signaling ◽  
Cancer Progression ◽  
Kras Mutation ◽  
Colorectal Cancer Progression

scholarly journals Signal Propagation in Protein Interaction Network during Colorectal Cancer Progression

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Yang Jiang ◽  
Tao Huang ◽  
Lei Chen ◽  
Yu-Fei Gao ◽  
Yudong Cai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Protein Interaction ◽  
Protein Interaction Network ◽  
Early Stage ◽  
Interaction Network ◽  
Signal Propagation ◽  
Cellular Systems ◽  
Propagation Path ◽  
Colorectal Cancer Progression

Colorectal cancer is generally categorized into the following four stages according to its development or serious degree: Dukes A, B, C, and D. Since different stage of colorectal cancer actually corresponds to different activated region of the network, the transition of different network states may reflect its pathological changes. In view of this, we compared the gene expressions among the colorectal cancer patients in the aforementioned four stages and obtained the early and late stage biomarkers, respectively. Subsequently, the two kinds of biomarkers were both mapped onto the protein interaction network. If an early biomarker and a late biomarker were close in the network and also if their expression levels were correlated in the Dukes B and C patients, then a signal propagation path from the early stage biomarker to the late one was identified. Many transition genes in the signal propagation paths were involved with the signal transduction, cell communication, and cellular process regulation. Some transition hubs were known as colorectal cancer genes. The findings reported here may provide useful insights for revealing the mechanism of colorectal cancer progression at the cellular systems biology level.

scholarly journals TP 53 mutation at early stage of colorectal cancer progression from two types of laterally spreading tumors

2016 ◽  
Vol 107 (6) ◽  
pp. 820-827 ◽  
Author(s):  
Eiji Sakai ◽  
Masaki Fukuyo ◽  
Keisuke Matsusaka ◽  
Ken Ohata ◽  
Noriteru Doi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Early Stage ◽  
Colorectal Cancer Progression ◽  
Laterally Spreading Tumors

scholarly journals Boosting Wnt activity during colorectal cancer progression through selective hypermethylation of Wnt signaling antagonists

BMC Cancer ◽  
2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Ana-Luisa Silva ◽  
Sarah N Dawson ◽  
Mark J Arends ◽  
Kiran Guttula ◽  
Nigel Hall ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Wnt Signaling ◽  
Cancer Progression ◽  
Colorectal Cancer Progression

Alterations in the number of motoneurons containing immunoreactive calcitonin gene-related peptide(CGRP)& choline acetyltransferase(ChAT) in the cervical spinal cord of the wobbler mouse during the development of the motoneuron disease

1995 ◽  
Vol 53 ◽  
pp. 970-971
Author(s):  
L. Vacca-Galloway ◽  
Y.Q. Zhang ◽  
P. Bose ◽  
S.H. Zhang
Keyword(s):  
Spinal Cord ◽  
Early Stage ◽  
Cervical Spinal Cord ◽  
Wild Type Mouse ◽  
Reflex Response ◽  
Mouse Strains ◽  
Behavioral Tests ◽  
Wobbler Mouse ◽  
Stage 4 ◽  
Stage 1

The Wobbler mouse (wr) has been studied as a model for inherited human motoneuron diseases (MNDs). Using behavioral tests for forelimb power, walking, climbing, and the “clasp-like reflex” response, the progress of the MND can be categorized into early (Stage 1, age 21 days) and late (Stage 4, age 3 months) stages. Age-and sex-matched normal phenotype littermates (NFR/wr) were used as controls (Stage 0), as well as mice from two related wild-type mouse strains: NFR/N and a C57BI/6N. Using behavioral tests, we also detected pre-symptomatic Wobblers at postnatal ages 7 and 14 days. The mice were anesthetized and perfusion-fixed for immunocytochemical (ICC) of CGRP and ChAT in the spinal cord (C3 to C5).Using computerized morphomety (Vidas, Zeiss), the numbers of IR-CGRP labelled motoneurons were significantly lower in 14 day old Wobbler specimens compared with the controls (Fig. 1). The same trend was observed at 21 days (Stage 1) and 3 months (Stage 4). The IR-CGRP-containing motoneurons in the Wobbler specimens declined progressively with age.

scholarly journals Decreased level of miR-1301 promotes colorectal cancer progression via activation of STAT3 pathway

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Fangfang Yang ◽  
Hua Wang ◽  
Bianbian Yan ◽  
Tong Li ◽  
Lulu Min ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Cancer Progression ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Aberrant Expression ◽  
Cell Migration And Invasion ◽  
Lovo Cells ◽  
Colorectal Cancer Progression

Abstract The molecular pathogenesis of colorectal cancer (CRC) has been widely investigated in recent years. Accumulating evidence has indicated that microRNA (miRNA) dysregulation participates in the processes of driving CRC initiation and progression. Aberrant expression of miR-1301 has been found in various tumor types. However, its role in CRC remains to be elucidated. In the present study, we identified miR-1301 was enriched in normal colorectal tissues and significantly down-regulated in CRC. Decreased level of miR-1301 strongly correlated with aggressive pathological characteristics, including advanced stage and metastasis. Bioinformatics and dual luciferase assay demonstrated that STAT3 is a direct target of miR-1301. Gain and loss-of-function assays showed that miR-1301 had no effect on cell proliferation. Overexpression of miR-1301 suppressed cell migration and invasion capacity of pSTA3-positive LoVo cells, but not pSTAT3-negative SW480 cells, while inhibition of miR-1301 consistently promoted cell migration and invasion in both cell lines. Additionally, miR-1301 inhibition restored the suppressed migration and invasion of STAT3- knockdown LoVo cells. MiR-1301 functioned as a tumor suppressor to modulate the IL6/STAT3 signaling pathway. In summary, this study highlights the significant role of miR- 1301/STAT3 axis in CRC metastasis.

scholarly journals Diethyldithiocarbamate-copper complex (CuET) inhibits colorectal cancer progression via miR-16-5p and 15b-5p/ALDH1A3/PKM2 axis-mediated aerobic glycolysis pathway

Oncogenesis ◽  
2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Xin Huang ◽  
Yichao Hou ◽  
Xiaoling Weng ◽  
Wenjing Pang ◽  
Lidan Hou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Copper Complex ◽  
Aerobic Glycolysis ◽  
Active Role ◽  
Downstream Effector ◽  
Glycolysis Pathway ◽  
Colorectal Cancer Progression

AbstractExploring novel anticancer drugs to optimize the efficacy may provide a benefit for the treatment of colorectal cancer (CRC). Disulfiram (DSF), as an antialcoholism drug, is metabolized into diethyldithiocarbamate-copper complex (CuET) in vivo, which has been reported to exert the anticancer effects on various tumors in preclinical studies. However, little is known about whether CuET plays an anti-cancer role in CRC. In this study, we found that CuET had a marked effect on suppressing CRC progression both in vitro and in vivo by reducing glucose metabolism. Mechanistically, using RNA-seq analysis, we identified ALDH1A3 as a target gene of CuET, which promoted cell viability and the capacity of clonal formation and inhibited apoptosis in CRC cells. MicroRNA (miR)-16-5p and 15b-5p were shown to synergistically regulate ALDH1A3, which was negatively correlated with both of them and inversely correlated with the survival of CRC patients. Notably, using co-immunoprecipitation followed with mass spectrometry assays, we identified PKM2 as a direct downstream effector of ALDH1A3 that stabilized PKM2 by reducing ubiquitination. Taken together, we disclose that CuET treatment plays an active role in inhibiting CRC progression via miR-16-5p and 15b-5p/ALDH1A3/PKM2 axis–mediated aerobic glycolysis pathway.

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