scholarly journals RIP140 Represses Intestinal Paneth Cell Differentiation and Interplays with SOX9 Signaling in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3192
Author(s):  
Antoine Gleizes ◽  
Mouna Triki ◽  
Sandrine Bonnet ◽  
Naomi Baccari ◽  
Gabriel Jimenez-Dominguez ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Differentiation ◽  
Paneth Cell ◽  
Wnt Signaling Pathway ◽  
Cell Lineage ◽  
Human Colon ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Sox9 Expression ◽  
Human Colon Cancer

RIP140 is a major transcriptional coregulator of gut homeostasis and tumorigenesis through the regulation of Wnt/APC signaling. Here, we investigated the effect of RIP140 on Paneth cell differentiation and its interplay with the transcription factor SOX9. Using loss of function mouse models, human colon cancer cells, and tumor microarray data sets we evaluated the role of RIP140 in SOX9 expression and activity using RT-qPCR, immunohistochemistry, luciferase reporter assays, and GST-pull down. We first evidence that RIP140 strongly represses the Paneth cell lineage in the intestinal epithelium cells by inhibiting Sox9 expression. We then demonstrate that RIP140 interacts with SOX9 and inhibits its transcriptional activity. Our results reveal that the Wnt signaling pathway exerts an opposite regulation on SOX9 and RIP140. Finally, the levels of expression of RIP140 and SOX9 exhibit a reverse response and prognosis value in human colorectal cancer biopsies. This work highlights an intimate transcriptional cross-talk between RIP140 and SOX9 in intestinal physiopathology.

scholarly journals Olaparib-mediated enhancement of 5-fluorouracil cytotoxicity in mismatch repair deficient colorectal cancer cells

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Helena de Castro e Gloria ◽  
Laura Jesuíno Nogueira ◽  
Patrícia Bencke Grudzinski ◽  
Paola Victória da Costa Ghignatti ◽  
Temenouga Nikolova Guecheva ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Mismatch Repair ◽  
Cell Cycle Progression ◽  
Combined Therapy ◽  
Combined Treatment ◽  
Human Colon ◽  
Human Colon Cancer

Abstract Background The advances in colorectal cancer (CRC) treatment include the identification of deficiencies in Mismatch Repair (MMR) pathway to predict the benefit of adjuvant 5-fluorouracil (5-FU) and oxaliplatin for stage II CRC and immunotherapy. Defective MMR contributes to chemoresistance in CRC. A growing body of evidence supports the role of Poly-(ADP-ribose) polymerase (PARP) inhibitors, such as Olaparib, in the treatment of different subsets of cancer beyond the tumors with homologous recombination deficiencies. In this work we evaluated the effect of Olaparib on 5-FU cytotoxicity in MMR-deficient and proficient CRC cells and the mechanisms involved. Methods Human colon cancer cell lines, proficient (HT29) and deficient (HCT116) in MMR, were treated with 5-FU and Olaparib. Cytotoxicity was assessed by MTT and clonogenic assays, apoptosis induction and cell cycle progression by flow cytometry, DNA damage by comet assay. Adhesion and transwell migration assays were also performed. Results Our results showed enhancement of the 5-FU citotoxicity by Olaparib in MMR-deficient HCT116 colon cancer cells. Moreover, the combined treatment with Olaparib and 5-FU induced G2/M arrest, apoptosis and polyploidy in these cells. In MMR proficient HT29 cells, the Olaparib alone reduced clonogenic survival, induced DNA damage accumulation and decreased the adhesion and migration capacities. Conclusion Our results suggest benefits of Olaparib inclusion in CRC treatment, as combination with 5-FU for MMR deficient CRC and as monotherapy for MMR proficient CRC. Thus, combined therapy with Olaparib could be a strategy to overcome 5-FU chemotherapeutic resistance in MMR-deficient CRC.

PEGylated Active Carbon Nanoparticles with Improved Dispersivity in Water and Potential Application in Lymphatic Targeted Therapy of Colorectal Cancer

2021 ◽  
Vol 66 ◽  
pp. 85-102
Author(s):  
Wen Kai Liu ◽  
Yuan Qing Song ◽  
Yan Ma ◽  
Xin Li ◽  
Peng Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Active Carbon ◽  
Potential Application ◽  
Carbon Nanoparticles ◽  
Drug Loading ◽  
Human Colon ◽  
Tumor Treatment ◽  
Human Colon Cancer ◽  
Pegylated Nanoparticles ◽  
Improved Stability

A series of PEGylated active carbon nanoparticles were fabricated with improved dispersity in water and were explored for their ability for carrying drugs and potential application in lymphatic targeted tracing and chemotherapy of colorectal cancer. The active carbon nanoparticles were oxidized in a mild condition with 30% H2O2 solution and then mPEG-NH2 was grafted to the nanoparticles. Compared with the original carbon nanoparticles, the oxidized and PEGylated nanoparticles all present improved stability and initial solubility in water and the PEGylated nanoparticles perform best. Size of the nanoparticles was well controlled in a rational area which can fulfill the requirement for lymphatic targeting. The PEGylated nanoparticles have excellent drug loading properties and allow for sustained release under physiological conditions. The MTT results show the drug-loaded nanoparticles can effectively kill SW480 cells (Human Colon Cancer Cells). These characteristics make the PEGylated nanoparticles become a promising candidate for using as drug-loaded powder for both lymphatic targeted tracing and chemo-therapy without using suspending agent in tumor treatment.

scholarly journals Correlation of GOLPH3 Gene with Wnt Signaling Pathway in Human Colon Cancer Cells

2016 ◽  
Vol 7 (8) ◽  
pp. 928-934 ◽  
Author(s):  
Cheng-Zhi Qiu ◽  
Ming-Zhen Wang ◽  
Wai-Shi Yu ◽  
Yan-Ta Guo ◽  
Chun-Xiao Wang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Wnt Signaling ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Human Colon Cancer Cells

scholarly journals Nei Endonuclease VIII-Like1 (NEIL1) Inhibits Apoptosis of Human Colorectal Cancer Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Wanjuan Xue ◽  
Yongcheng Liu ◽  
Ningning Xin ◽  
Jiyu Miao ◽  
Juan Du ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Human Colon ◽  
Caspase 9 ◽  
Human Colon Cancer ◽  
Expression Levels ◽  
Colorectal Cancer Cells ◽  
Human Colorectal Cancer Cells

The study is aimed at investigating the role of Nei endonuclease VIII-like1 (NEIL1) in the pathogenesis of colorectal cancer (CRC). The human CRC (HCT116 and SW480) cells were subjected to the siRNA silencing and recombinant plasmid overexpression of NEIL1. Transfection of siNEIL1 significantly inhibited the cell growth. It also increased the Bax expression levels, while it decreased the Bcl-2 expression levels in human CRC cells, leading the Bax/Bcl-2 balance toward apoptosis. Moreover, the apoptosis was promoted through the caspase-9 signaling pathway. One the other hand, high expression of NEIL1 promoted the cell viability and reduced the apoptosis, inducing the balance of Bax/Bcl-2 in the human colon cancer cells to be antiapoptotic. In addition, the caspase-9 signaling pathway inhibited apoptosis, contrary to the results obtained by downregulating NEIL1 expression. Furthermore, NEIL1 was negatively regulated by miR-7-5p, indicating that miR-7-5p inhibited the NEIL1 expression after transcription. Overexpression of miR-7-5p reversed the effects of NEIL1 on these CRC cells. In conclusion, NEIL1 promotes the proliferation of CRC cells, which is regulated negatively by miR-7-5p. These findings suggest that NEIL1 is a potential therapeutic target for CRC.

scholarly journals Intestinal Neurod1 expression impairs paneth cell differentiation and promotes enteroendocrine lineage specification

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hui Joyce Li ◽  
Subir K. Ray ◽  
Ning Pan ◽  
Jody Haigh ◽  
Bernd Fritzsch ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Epithelial Cells ◽  
Cell Fate ◽  
Intestinal Epithelial Cells ◽  
Paneth Cell ◽  
Substantial Reduction ◽  
Ectopic Expression ◽  
Cell Lineage ◽  
Intestinal Epithelial ◽  
Conditional Expression

AbstractTranscription factor Neurod1 is required for enteroendocrine progenitor differentiation and maturation. Several earlier studies indicated that ectopic expression of Neurod1 converted non- neuronal cells into neurons. However, the functional consequence of ectopic Neurod1 expression has not been examined in the GI tract, and it is not known whether Neurod1 can similarly switch cell fates in the intestine. We generated a mouse line that would enable us to conditionally express Neurod1 in intestinal epithelial cells at different stages of differentiation. Forced expression of Neurod1 throughout intestinal epithelium increased the number of EECs as well as the expression of EE specific transcription factors and hormones. Furthermore, we observed a substantial reduction of Paneth cell marker expression, although the expressions of enterocyte-, tuft- and goblet-cell specific markers are largely not affected. Our earlier study indicated that Neurog3+ progenitor cells give rise to not only EECs but also Goblet and Paneth cells. Here we show that the conditional expression of Neurod1 restricts Neurog3+ progenitors to adopt Paneth cell fate, and promotes more pronounced EE cell differentiation, while such effects are not seen in more differentiated Neurod1+ cells. Together, our data suggest that forced expression of Neurod1 programs intestinal epithelial cells more towards an EE cell fate at the expense of the Paneth cell lineage and the effect ceases as cells mature to EE cells.

scholarly journals Colorectal Cancer Study with Nanostructured Sensors: Tumor Marker Screening of Patient Biopsies

Nanomaterials ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 606 ◽  
Author(s):  
Michele Astolfi ◽  
Giorgio Rispoli ◽  
Gabriele Anania ◽  
Veronica Nevoso ◽  
Elena Artioli ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Principal Component ◽  
Human Colon ◽  
Diagnostic Methods ◽  
Human Colon Cancer ◽  
Discrimination Power ◽  
Tissue Samples ◽  
Chemoresistive Sensors ◽  
One Year ◽  
Nanostructured Sensors

Despite the great progress in screening techniques and medical treatments, colorectal cancer remains one of the most widespread cancers in both sexes, with a high death rate. In this work, the volatile compounds released from human colon cancer tissues were detected by a set of four different chemoresistive sensors, made with a nanostructured powder of metal-oxide materials, inserted into an innovative patented device. The sensor responses to the exhalation of a primary cancer sample and of a healthy sample (both of the same weight, collected during colorectal surgery from the intestine of the same patient) were statistically analyzed. The sensors gave reversible, reproducible, and fast responses for at least one year of continuous use, making them quite superior in respect to the existing diagnostic methods. Preliminary results obtained using principal component analysis of the sensor responses to samples removed from 13 patients indicate that the nanostructured sensors employed in this study were able to distinguish between healthy and tumor tissue samples with coherent responses (the discrimination power of the most sensitive sensor was about 17%), highlighting a strong potential for clinical practice.

scholarly journals Animal models of gastrointestinal and liver diseases. New mouse models for studying dietary prevention of colorectal cancer

2014 ◽  
Vol 307 (3) ◽  
pp. G249-G259 ◽  
Author(s):  
James C. Fleet
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Mouse Models ◽  
Human Colon ◽  
Low Grade ◽  
Preclinical Models ◽  
Dietary Interventions ◽  
Single Model ◽  
Human Colon Cancer ◽  
Molecular Etiology

Colorectal cancer is a heterogeneous disease that is one of the major causes of cancer death in the U.S. There is evidence that lifestyle factors like diet can modulate the course of this disease. Demonstrating the benefit and mechanism of action of dietary interventions against colon cancer will require studies in preclinical models. Many mouse models have been developed to study colon cancer but no single model can reflect all types of colon cancer in terms of molecular etiology. In addition, many models develop only low-grade cancers and are confounded by development of the disease outside of the colon. This review will discuss how mice can be used to model human colon cancer and it will describe a variety of new mouse models that develop colon-restricted cancer as well as more advanced phenotypes for studies of late-state disease.

Identification of polyphenol from Ziziphi spinosae semen against human colon cancer cells and colitis-associated colorectal cancer in mice

2020 ◽  
Vol 11 (9) ◽  
pp. 8259-8272
Author(s):  
Shuhua Shan ◽  
Yue Xie ◽  
Chengying Zhang ◽  
Bin Jia ◽  
Hanqing Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Pharmacological Property ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Human Colon Cancer Cells

Spinosin derived from homology of medicine and food-zizyphi spinosi semen (ZSS) exhibits a new pharmacological property against colon cancer.

scholarly journals LukS-PV-Regulated MicroRNA-125a-3p Promotes THP-1 Macrophages Differentiation and Apoptosis by Down-Regulating NF1 and Bcl-2

2017 ◽  
Vol 44 (3) ◽  
pp. 1093-1105 ◽  
Author(s):  
Xiao-Xi Sun ◽  
Shan-Shan Zhang ◽  
Chun-Yang Dai ◽  
Jing Peng ◽  
Qing Pan ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Cellular Differentiation ◽  
Target Genes ◽  
B Cell Lymphoma ◽  
Neurofibromatosis Type ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Leukaemia Cell Line ◽  
Reporter Assays

Background/Aims: LukS-PV is a component of Panton-Valentine leukocidin (PVL). We have previously demonstrated that LukS-PV potently promoted differentiation and induced apoptosis in THP-1 cells. However, the precise mechanisms of these actions remain unknown. MicroRNAs (miRs) play important roles in cellular differentiation and apoptosis. This study aimed to investigate the role of miR-125a-3p in LukS-PV-regulated differentiation and apoptosis and its underlying mechanism in THP-1 cells. Methods: MicroRNA profiling analyses were conducted to determine differential miRNA expression levels in THP-1 cells treated with LukS-PV. Cell differentiation and apoptosis were measured in THP-1 cells by gain-of-function and loss-of-function experiments. Bioinformatics analysis and luciferase reporter assays were used to confirm the targets of miR-125a-3p. The effects of the miR-125a-3p targets on cellular differentiation were determined by knocking them down. Results: MiR-125a-3p was up-regulated after treating the human monocytic leukaemia cell line THP-1 with LukS-PV. In addition, miR-125a-3p positively regulated apoptosis and differentiation in THP-1 cells treated with LukS-PV. Concordantly, luciferase reporter assays confirmed that neurofibromatosis type 1 (NF1) and B-cell lymphoma 2 (Bcl-2) were direct target genes of miR-125a-3p. Moreover, NF1 knockdown in THP-1 cells significantly promoted differentiation in vitro. Finally, the extracellular signal-regulated kinase (ERK) pathway, a downstream target of NF1, was activated after NF1 knockdown. Conclusions: These findings confirm that miR-125a-3p is involved in LukS-PV-mediated cell differentiation and apoptosis in THP-1 cells.

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