Hypoxia Facilitates the Proliferation of Colorectal Cancer Cells by Inducing Cancer-associated Fibroblast-derived IL6.

2021 ◽  
Author(s):  
Ying Xu ◽  
Rong Kuai ◽  
Yimin Chu ◽  
Lu Zhou ◽  
Hai-qin Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Tumor Development ◽  
Cancer Associated Fibroblast ◽  
Stat3 Signaling ◽  
Colorectal Cancer Cells ◽  
Cancer Tissues ◽  
Development Methods ◽  
Multiplex Cytokine ◽  
Common Malignancy

Abstract Background: Colorectal cancer (CRC) is most common malignancy worldwide, and its underlying molecular mechanisms remain largely unexplored. Accumulating evidences indicate Cancer-Associated Fibroblasts (CAFs), abundant stromal cell population in the tumor microenvironment, play a key role in tumor development. Methods: We have successfully isolated CAFs and paired normal fibroblasts (NFs) from colorectal cancer tissues (n=10). By using multiplex cytokine profiling assay, we have identified IL-6 as a major cytokine released by CAFs. Coculturing of CAFs with CRC cell lines HCT116 or SW480 increase IL-6 release, and the secretion by CAFs can be further enhanced under hypoxia. By using CCK-8 assay, we have found HCT116 or SW480 cells treated with culture medium from CAFs, IL-6 or hypoxia showed a significant cell growth compared to control cells (P<0.01). Results: Mechanistically, we have found hypoxia can enhanced effect of IL-6/STAT3 signaling on CRC cells, in part, throughHIF-1a targets PKM2. Conclusions: In conclusion, our data clearly proposes the interconnected mechanisms for a constitutive activation of STAT3 signalby CAFs-derived IL-6 under hypoxia in colorectal cancer. The pharmacological inhibition of STAT3, PKM2 or HIF-1α can significantly reduce oncogenic effect of IL-6, providing a potential therapeutic target for CRC patients.Trail registration: Not applicable

scholarly journals LMNB2 promotes the progression of colorectal cancer by silencing p21 expression

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Chen-Hua Dong ◽  
Tao Jiang ◽  
Hang Yin ◽  
Hu Song ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Gene Set Enrichment Analysis ◽  
Molecular Therapy ◽  
Cycle Progression ◽  
Cancer Tissues

AbstractColorectal cancer is the second common cause of death worldwide. Lamin B2 (LMNB2) is involved in chromatin remodeling and the rupture and reorganization of nuclear membrane during mitosis, which is necessary for eukaryotic cell proliferation. However, the role of LMNB2 in colorectal cancer (CRC) is poorly understood. This study explored the biological functions of LMNB2 in the progression of colorectal cancer and explored the possible molecular mechanisms. We found that LMNB2 was significantly upregulated in primary colorectal cancer tissues and cell lines, compared with paired non-cancerous tissues and normal colorectal epithelium. The high expression of LMNB2 in colorectal cancer tissues is significantly related to the clinicopathological characteristics of the patients and the shorter overall and disease-free cumulative survival. Functional analysis, including CCK8 cell proliferation test, EdU proliferation test, colony formation analysis, nude mouse xenograft, cell cycle, and apoptosis analysis showed that LMNB2 significantly promotes cell proliferation by promoting cell cycle progression in vivo and in vitro. In addition, gene set enrichment analysis, luciferase report analysis, and CHIP analysis showed that LMNB2 promotes cell proliferation by regulating the p21 promoter, whereas LMNB2 has no effect on cell apoptosis. In summary, these findings not only indicate that LMNB2 promotes the proliferation of colorectal cancer by regulating p21-mediated cell cycle progression, but also suggest the potential value of LMNB2 as a clinical prognostic marker and molecular therapy target.

scholarly journals Lichen-Derived Depsides and Depsidones Modulate the Nrf2, NF-κB and STAT3 Signaling Pathways in Colorectal Cancer Cells

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4787
Author(s):  
Katarzyna Papierska ◽  
Violetta Krajka-Kuźniak ◽  
Jarosław Paluszczak ◽  
Robert Kleszcz ◽  
Marcin Skalski ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Secondary Metabolites ◽  
Signaling Pathways ◽  
Opposite Effect ◽  
Target Genes ◽  
Rt Pcr ◽  
Stat3 Signaling ◽  
Activation Of Transcription ◽  
Colorectal Cancer Cells ◽  
Pathway Networks

The study aimed to evaluate the possible modulation of Nrf2, NF-ĸB and STAT3 signaling pathways in the colorectal cancer (CRC) cells line DLD-1 and HCT116 by secondary metabolites of lichens. An attempt was made to indicate the most promising targets in these signaling pathways. Attention was also paid to the effects of the compounds tested on CRC cells using anakoinosis—that is, simultaneous analysis of several signaling pathways. The effects of the tested natural compounds on the activity of selected transcriptional factors related to CRC were analyzed by Western blot and RT-PCR assays. The highest activity against CRC cells was shown by physodic and salazinic acids from the studied secondary metabolites of lichens. As a result, an increase in the activation of transcription factor Nrf2 and the expression of its selected target genes was observed. Physodic and salazinic acids induced the opposite effect in relation to the NF-κB and STAT3 pathways. These results confirmed our earlier observations that lichen-derived compounds have the ability to modulate signaling pathway networks. While caperatic acid affected Wnt/β-catenin to the most extent, salazinic acid was the most potent modulator of Nrf2, NF-κB and STAT3 pathways. Physodic acid seemed to affect all the investigated pathways.

CircABCC4 Regulates the Proliferation, Migration, and Invasion of Colorectal Cancer SW620 Cells by Targeting Micro RNA-216a-3p

2021 ◽  
Vol 11 (3) ◽  
pp. 548-552
Author(s):  
Yiqian Li ◽  
Haofeng Yuan ◽  
Yibin Chen ◽  
Baoqi Xu ◽  
Yanhong Zhang
Keyword(s):  
Colorectal Cancer ◽  
Micro Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Human Colorectal Cancer ◽  
Cell Behaviors ◽  
Colorectal Cancer Cells ◽  
Sw620 Cells ◽  
Cancer Tissues ◽  
Dual Luciferase Reporter Assay

This work investigates the effect of circABCC4 on the proliferation, migration, and invasion of colorectal cancer SW620 cells; circABCC4’s regulation of miR-216a-3p is also studied. qRT-PCR was used to measure the levels of circABCC4 and miR-216a-3p in colorectal cancer and adjacent tissues. The human colorectal cancer SW620 cells were transfected with different constructs of circABCC4 or miR-216a-3p or both to study their interactions and combined effects on cell behavior. A dual-luciferase reporter experiment tested the targeted relationship between circABCC4 to miR-216a-3p. Furthermore, the behaviors of SW620 cells, such as cell viability, migration, and invasion, were investigated. Also, the proteins related to cell behaviors were investigated with western blotting. Our results showed that colorectal cancer tissues had a higher level of circABCC4 but a lower level miR-216a-3p. The increased level of circABCC4 and the reduced level of miR-216a-3p had analogous influences on the behaviors of SW620 cells, resulting in reduced cell proliferation, migration, and invasion; the levels of related protein were also decreased. Moreover, we found that disrupting miR-548c-3p could reverse the influence of inhibiting circABCC4 on SW620 cells. In addition, the dual-luciferase reporter assay results confirmed the targeting of miR-216a-3p by circABCC4. These data demonstrate that the silencing of circABCC4 may inhibit the proliferation, migration, and invasion of colorectal cancer cells by upregulating miR-548c-3p.

scholarly journals The Molecular Mechanisms Involved in the miR-29a-5p/STAT3 Signaling Loop in Ulcerative Colitis–Associated Colorectal Cancer Still Remain Unclear

2020 ◽  
Vol 26 (8) ◽  
pp. e87-e87
Author(s):  
Ion Cristóbal ◽  
Juan Madoz-Gúrpide ◽  
Federico Rojo ◽  
Jesús García-Foncillas
Keyword(s):  
Colorectal Cancer ◽  
Ulcerative Colitis ◽  
Molecular Mechanisms ◽  
Stat3 Signaling

scholarly journals Helicteric Acid, Oleanic Acid, and Betulinic Acid, Three Triterpenes fromHelicteres angustifoliaL., Inhibit Proliferation and Induce Apoptosis in HT-29 Colorectal Cancer Cells via Suppressing NF-κB and STAT3 Signaling

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Dan Su ◽  
Yu-qiao Gao ◽  
Wei-bo Dai ◽  
Ying Hu ◽  
Yan-fen Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Betulinic Acid ◽  
Biological Activities ◽  
Colorectal Tumor ◽  
Antitumor Effects ◽  
Chinese Medicinal Herb ◽  
Stat3 Signaling ◽  
Colorectal Cancer Cells ◽  
Ht 29

Colorectal cancer (CRC) is one of the most common malignancies and most frequent cause of cancer death worldwide. The activation of both NF-κB and STAT3 signaling and the crosstalk between them play an important role in colorectal tumor.Helicteres angustifoliaL. is a type of commonly used Chinese medicinal herb and possesses a wide variety of biological activities. In the present study, we investigate the effects of three triterpenes fromH. angustifolia(HT) such as helicteric acid (HA), oleanic acid (OA), and betulinic acid (BA), on inhibiting CRC progression. Our results showed that HT extracts could decrease proliferation and induce apoptosis in HT-29 colorectal cancer cells. Moreover, HT extracts could suppress LPS-triggered phosphorylation of IKK, IκB, and NF-κB, attenuate IL-6-induced phosphorylation of JAK2 and STAT3, and suppress the expression of c-Myc, cyclin-D1, and BCL-xL, the downstream gene targets of NF-κB and STAT3. Therefore, HT extracts showed potent therapeutic and antitumor effects on CRC via inhibiting NF-κB and STAT3 signaling.

scholarly journals 43P Molecular mechanisms related to chemoresistance of colorectal cancer cells

2020 ◽  
Vol 31 ◽  
pp. S1230
Author(s):  
B. Novoa Díaz ◽  
A.O. Zwenger ◽  
P.M. Carriere ◽  
M.J. Martin ◽  
N. Calvo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Colorectal Cancer Cells

scholarly journals Molecular mechanisms of action and prediction of response to oxaliplatin in colorectal cancer cells

2004 ◽  
Vol 91 (11) ◽  
pp. 1931-1946 ◽  
Author(s):  
D Arango ◽  
A J Wilson ◽  
Q Shi ◽  
G A Corner ◽  
M J Arañes ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Mechanisms Of Action ◽  
Prediction Of Response ◽  
Colorectal Cancer Cells

scholarly journals TCN1 Deficiency Inhibits The Malignancy of Colorectal Cancer Cells By Regulating The ITGB4 Pathway

2021 ◽  
Author(s):  
Xinqiang Zhu ◽  
Xuetong Jiang ◽  
Qinglin Zhang ◽  
Hailong Huang ◽  
Xiaohong Shi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Function Analysis ◽  
Hct116 Cell ◽  
Tumor Xenograft ◽  
Integrin Subunit ◽  
Filamin A ◽  
Loss Of Function ◽  
Colorectal Cancer Cells

Abstract Background: This study aimed to investigate the biological function and regulatory mechanism of TCN1 in colorectal cancer (CRC). Methods: We studied the biological functions of TCN1 using gain-of-function and loss-of-function analysis in HCT116 cell lines, and examined the effects of TCN1 on the proliferation, apoptosis, and invasion of CRC cells and determined its potential molecular mechanisms using CRC lines and mouse xenotransplantation models. Tumor xenograft and tumor metastasis studies were performed to detect the tumorigenicity and metastasis of cells in vivo. Results: TCN1-knockdown attenuated CRC cell proliferation, invasion and promoted cell apoptosis. Overexpression of TCN1 yielded the opposite effects. In addition, TCN1-knockdown HCT116 cells failed to form metastatic foci in the peritoneum after intravenous injection. Molecular mechanism studies showed that TCN1 interacts with integrin subunit β4 (ITGB4) to positively regulate the expression of ITGB4. TCN1-knockdown promoted the degradation of ITGB4 and increased the instability of ITGB4 and filamin A (FLNA). Downregulation of ITGB4 at the protein level resulted in the disassociation of the ITGB4/PLEC complex, leading to cytoskeletal damage. Conclusion: TCN1 might exert oncogenic role in CRC via regulating the ITGB4 signaling pathway.

scholarly journals A New Light on Potential Therapeutic Targets for Colorectal Cancer Treatment

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1438
Author(s):  
Wei-Lun Tsai ◽  
Chih-Yang Wang ◽  
Yu-Cheng Lee ◽  
Wan-Chun Tang ◽  
Gangga Anuraga ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Tumor Development ◽  
Gene Expression Omnibus ◽  
Different Types ◽  
Geo Dataset ◽  
Non Coding Rnas ◽  
Poor Outcomes ◽  
Upregulated Genes

The development and progression of colorectal cancer (CRC) involve changes in genetic and epigenetic levels of oncogenes and/or tumor suppressors. In spite of advances in understanding of the molecular mechanisms involved in CRC, the overall survival rate of CRC still remains relatively low. Thus, more research is needed to discover and investigate effective biomarkers and targets for diagnosing and treating CRC. The roles of long non-coding RNAs (lncRNAs) participating in various aspects of cell biology have been investigated and potentially contribute to tumor development. Our recent study also showed that CRNDE was among the top 20 upregulated genes in CRC clinical tissues compared to normal colorectal tissues by analyzing a Gene Expression Omnibus (GEO) dataset (GSE21815). Although CRNDE is widely reported to be associated with different types of cancer, most studies of CRNDE were limited to examining regulation of its transcription levels, and in-depth mechanistic research is lacking. In the present study, CRNDE was found to be significantly upregulated in CRC patients at an advanced TNM stage, and its high expression was correlated with poor outcomes of CRC patients. In addition, we found that knocking down CRNDE could reduce lipid accumulation through the miR-29b-3p/ANGPTL4 axis and consequently induce autophagy of CRC cells.

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