scholarly journals Heterogenous Nuclear Ribonucleoprotein H1 Promotes Colorectal Cancer Progression through the Stabilization of mRNA of Sphingosine-1-Phosphate Lyase 1

2020 ◽  
Vol 21 (12) ◽  
pp. 4514 ◽  
Author(s):  
Keitaro Takahashi ◽  
Mikihiro Fujiya ◽  
Hiroaki Konishi ◽  
Yuki Murakami ◽  
Takuya Iwama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Growth ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Colorectal Cancer Cell ◽  
Colorectal Cancer Cells ◽  
Cell Progression ◽  
Sphingosine 1 Phosphate ◽  
Nuclear Ribonucleoprotein

The oncogenic properties of heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) have been reported, although the tumor-promoting mechanism remains unclear. We herein report the mechanism underlying colorectal cancer cell progression mediated by hnRNP H1. The growth of colorectal cancer cells was suppressed by hnRNP H1 downregulation. A terminal deoxynucleotidyl transferase dUTP nick-end labeling assay revealed the anti-apoptotic effect of hnRNP H1 in colorectal cancer cells. An RNA immunoprecipitation assay revealed that hnRNP H1 bound to sphingosine-1-phosphate lyase 1 (SGPL1). Reverse transcription-polymerase chain reaction revealed the high expression of hnRNP H1 mRNA in colorectal cancer cells and Spearman’s rank correlation coefficient showed a strong positive correlation between hnRNP H1 mRNA and SGPL1 mRNA. An siRNA of hnRNP H1 decreased SGPL1 mRNA expression in colorectal cancer cells, but not in non-tumorous cells. These findings suggested that hnRNP H1 increased SGPL1 mRNA expression specifically in cancer cells through direct binding. Targeted knockdown of hnRNP H1 or SGPL1 with siRNAs upregulated p53 phosphorylation and p53-associated molecules, resulting in cell growth inhibition, while hnRNP H1 upregulated the mRNA of SGPL1 and inhibited p53 activation, thereby promoting tumor cell growth. This is a novel mechanism underlying colorectal cancer cell progression mediated by hnRNP H1–SGPL1 mRNA stabilization.

scholarly journals An Integrated Bioinformatics Analysis Repurposes an Antihelminthic Drug Niclosamide for Treating HMGA2-Overexpressing Human Colorectal Cancer

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1482 ◽  
Author(s):  
Leung ◽  
Chou ◽  
Huang ◽  
Yang
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Gene Signature ◽  
Cancer Cell Lines ◽  
Colorectal Cancer Cell ◽  
Sequencing Analysis ◽  
Colorectal Cancer Cells ◽  
Colorectal Cancer Cell Lines

Aberrant overexpression of high mobility group AT-hook 2 (HMGA2) is frequently found in cancers and HMGA2 has been considered an anticancer therapeutic target. In this study, a pan-cancer genomics survey based on Cancer Cell Line Encyclopedia (CCLE) and The Cancer Genome Atlas (TCGA) data indicated that HMGA2 was mainly overexpressed in gastrointestinal cancers including colorectal cancer. Intriguingly, HMGA2 overexpression had no prognostic impacts on cancer patients’ overall and disease-free survivals. In addition, HMGA2-overexpressing colorectal cancer cell lines did not display higher susceptibility to a previously identified HMGA2 inhibitor (netroposin). By microarray profiling of HMGA2-driven gene signature and subsequent Connectivity Map (CMap) database mining, we identified that S100 calcium-binding protein A4 (S100A4) may be a druggable vulnerability for HMGA2-overexpressing colorectal cancer. A repurposing S100A4 inhibitor, niclosamide, was found to reverse the HMGA2-driven gene signature both in colorectal cancer cell lines and patients’ tissues. In vitro and in vivo experiments validated that HMGA2-overexpressing colorectal cancer cells were more sensitive to niclosamide. However, inhibition of S100A4 by siRNAs and other inhibitors was not sufficient to exert effects like niclosamide. Further RNA sequencing analysis identified that niclosamide inhibited more cell-cycle-related gene expression in HMGA2-overexpressing colorectal cancer cells, which may explain its selective anticancer effect. Together, our study repurposes an anthelminthic drug niclosamide for treating HMGA2-overexpression colorectal cancer.

scholarly journals A Low-Cost and Portable Smart Instrumentation for Detecting Colorectal Cancer Cells

2019 ◽  
Vol 9 (17) ◽  
pp. 3510 ◽  
Author(s):  
Mohammad Wajih Alam ◽  
Khan A. Wahid ◽  
Md. Fahmid Islam ◽  
Wendy Bernhard ◽  
Clarence R. Geyer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Mammalian Cells ◽  
Imaging System ◽  
Low Cost ◽  
Colorectal Cancer Cell ◽  
Colorectal Cancer Cell Line ◽  
Visible Range ◽  
Colorectal Cancer Cells

Fluorescence imaging is a well-known method for monitoring fluorescence emitted from the subject of interest and provides important insights about cell dynamics and molecules in mammalian cells. Currently, many solutions exist for measuring fluorescence, but the application methods are complex and the costs are high. This paper describes the design and development of a low-cost, smart and portable fluorimeter for the detection of colorectal cancer cell expressing IRFP702. A flashlight is used as a light source, which emits light in the visible range and acts as an excitation source, while a photodiode is used as a detector. It also uses a longpass filter to only allow the wavelength of interest to pass from the cultured cell. It eliminates the need of both the dichroic mirror and excitation filter, which makes the developed device low cost, compact and portable as well as lightweight. The custom-built sample chamber is black in color to minimize interference and is printed with a 3D printer to accommodate the detector circuitry. An established colorectal cancer cell line (human colorectal carcinoma (HCT116)) was cultured in the laboratory environment. A near-infrared fluorescent protein IRFP702 was expressed in the colorectal cancer cells that were used to test the proof-of-concept. The fluorescent cancer cells were first tested with a commercial imaging system (Odyssey® CLx) and then with the developed prototype to validate the result in a preclinical setting. The developed fluorimeter is versatile as it can also be used to detect multiple types of cancer cells by simply replacing the filters based on the fluorophore.

scholarly journals Interleukin Receptor Antagonist Inhibits Matastatic Potential by Down-Regulating CXCL12/CXCR4 Signaling Axis in Colorectal Cancer

2021 ◽  
Author(s):  
Jiachi Ma ◽  
Wanqing Liang ◽  
Yaosheng Qiang ◽  
Lei Li ◽  
Jun Du ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Stromal Cells ◽  
Metastatic Potential ◽  
Colorectal Cancer Cell ◽  
Colorectal Cancer Cells ◽  
Ht 29 ◽  
High Liver

Abstract Background: The aim of this study was to investigate the co-operative role of CXCR4/ CXCL12 axis and IL-1Ra in metastatic processes mechanism by interactions between colorectal cancer cells and stromal cells in their microenvironment. Methods: Expression of IL-1a, CXCL12 and CXCR4 mRNA and proteins were determined by RT-PCR and Western blot. The effect of secreted level of CXCL12 by IL-1Ra on fibroblasts was measured by ELISA. CXCL12 regulate metastatic potential of colorectal cancer was evaluated by proliferation, invasion and angiogenesis assays, respectively, in which invasion and angiogenesis assays used an in vitro system consisting of co-cultured colorectal cells and stromal cells. Results: IL-1a was expressed in high liver metastatic colorectal cancer cell lines (HT-29 and WiDr). The colorectal cancer cell-derived IL-1a and rIL-1a significantly promoted CXCL12 expression by fibroblasts, and this enhancing effect can be significantly inhibited by IL-1Ra (P<0.01). CXCL12 not only enhanced the migration and proliferation of human umbilical vein endothelial cells (HUVECs), but also significantly enhanced angiogenesis (P<0.01). Furthermore, the high liver-metastatic colorectal cancer cell line (HT-29), which secretes IL-1a, significantly enhanced angiogenesis compared to the low liver-metastatic cell line (CaCo-2), which does not produce IL-1a (P<0.01). On the contrary, IL-1Ra can significantly inhibit migration, proliferation and angiogenesis (P<0.01). Conclusion: Autocrine IL-1a and paracrine CXCL12 co-enhances the metastatic potential of colorectal cancer cells; IL-1Ra can inhibit the metastatic potential of colorectal cancer cells via decrease IL-1a/CXCR4/CXCL12 signaling pathways.

scholarly journals Surface-bound galectin-4 regulates gene transcription and secretion of chemokines in human colorectal cancer cell lines

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769168 ◽  
Author(s):  
U Subrahmanyeswara Rao ◽  
Prema S Rao
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Surface ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Colorectal Cancer Cell ◽  
Colorectal Tumorigenesis ◽  
Colorectal Cancer Cells ◽  
Colorectal Cancer Cell Lines

One long-term complication of chronic intestinal inflammation is the development of colorectal cancer. However, the mechanisms linking inflammation to the colorectal tumorigenesis are poorly defined. Previously, we have demonstrated that galectin-4 is predominantly expressed in the luminal epithelia of the gastrointestinal tract, and its loss of expression plays a key role in the colorectal tumorigenesis. However, the mechanism by which galectin-4 regulates inflammation-induced tumorigenesis is unclear. Here, we show that galectin-4 secreted by the colorectal cancer cell lines was bound to the cell surface. Neutralization of surface-bound galectin-4 with anti-galectin-4 antibody resulted in increased cell proliferation with concomitant secretion of several chemokines into the extracellular medium. Neutralization of the surface-bound galectin-4 also resulted in the up-regulation of transcription of 29 genes, several of which are components of multiple inflammation signaling pathways. In an alternate experiment, binding of recombinant galectin-4 protein to cell surface of the galectin-4-negative colorectal cancer cells resulted in increased p27, and decreased cyclin D1 and c-Myc levels, leading to cell cycle arrest and apoptosis. Together, these data demonstrated that surface-bound galectin-4 is a dual function protein—down-regulating cell proliferation and chemokine secretion in galectin-4-expressing colorectal cancer cells on one hand and inducing apoptosis in galectin-4-negative colorectal cancer cells on the other hand.

scholarly journals HIPK3 Inhibition by Exosomal hsa-miR-101-3p Is Related to Metabolic Reprogramming in Colorectal Cancer

2022 ◽  
Vol 11 ◽  
Author(s):  
Lihuiping Tao ◽  
Changliang Xu ◽  
Weixing Shen ◽  
Jiani Tan ◽  
Liu Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Colorectal Cancer Cell ◽  
Target Analysis ◽  
Exosomal Mirnas ◽  
Colorectal Cancer Cell Lines

BackgroundExosomes are extracellular vesicles secreted by most cells to deliver functional cargoes to recipient cells. MicroRNAs (miRNAs) constitute a significant part of exosomal contents. The ease of diffusion of exosomes renders them speedy and highly efficient vehicles to deliver functional molecules. Cancer cells secrete more exosomes than normal cells. Reports have showed that exosomal miRNAs of cancer cells facilitate cancer progression. Yet the complexity of cancer dictates that many more functional exosomal miRNAs remain to be discovered.MethodsIn this study, we analyzed miRNA expression profiles of tissue and plasma exosome samples collected from 10 colorectal cancer (CRC) patients and 10 healthy individuals. We focused on hsa-miR-101-3p (101-3p), a profoundly up-regulated miRNA enriched in plasma exosomes of patients bearing CRC. We performed target analysis of 101-3p and pursued functional studies of this microRNA in two colorectal cancer cell lines, namely HCT116 and SW480.ResultsOur results indicated that inhibiting 101-3p slowed cell growth and retarded cell migration in vivo in two colorectal cancer cell lines. Target analysis showed that Homeodomain-interacting protein kinase (HIPK3) is a target of miR-101-3p. HCT116 and SW480 cells stably overexpressing HIPK3 showed increased level of phosphorylated FADD, as well as retarded cell growth, migration, and increased sensitivity to 5-FU. In-depth analysis revealed increased mitochondrial membrane potential upon HIPK3 overexpression along with increased production of reactive oxygen species, number of mitochondria, and expression of respiratory complexes. Measurements of glycolytic parameters and enzymes revealed decreased level of glycolysis upon HIPK3 overexpression in these two cell lines. Xenograft model further confirmed a profoundly improved potency of the synergistic treatment combining both 5-FU and 101-3p inhibitor compared to 5-FU alone.ConclusionThis study unraveled an oncogenic nature of the exosomal 101-3p and suggested a relationship between the 101-3p-HIPK3 axis and metabolic homeostasis in colorectal cancer. Expression level of 101-3p is positively correlated with glycolytic capacity in CRC and therefore 101-3p itself is an oncomiR. Combining 101-3p inhibitor with chemotherapeutic agents is an effective strategy against CRC.

scholarly journals Sponges from North Borneo and their bioactivity against human colorectal cancer cells

2018 ◽  
Vol 2 ◽  
pp. 40-47
Author(s):  
Yoong Soon Yong ◽  
Swee-Cheng Lim ◽  
Ping-Chin Lee ◽  
Yee-Soon Ling
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Marine Sponges ◽  
Colorectal Cancer Cell ◽  
Human Colorectal Cancer ◽  
Cytotoxicity Activity ◽  
North Borneo ◽  
Wide Range ◽  
Colorectal Cancer Cells

Invertebrates are a major reservoir for numerous cytotoxic compounds that are used to defence themselves against prey and adaptation towards the environment. Throughout the years, numerous studies discovered from sponge extracts were effective against a wide range of cancer cells. In this study, 23 sponges comprising of some 19 species were collected from Northeast Borneo. Sponges were treated and extracted using modified Folch extraction method, followed by cytotoxicity assay to determine their effectiveness against different colorectal cancer cells. From the results, Monanchora clathrate, Dysidea sp., and Jaspis sp. were found to possess different degrees of cytotoxicity against wide range of human colorectal cancer cell. Monanchora clathrate (KDT07), Dysidea sp. (KDT09), and Jaspis sp. (KDT18) are among the demosponges which possess significant cytotoxicity against colorectal cancer cell lines, including HCT116, LoVo, SW480, and SW620. Besides, we found that environmental factors tend to alter chemical yield from the different species under the same genera. Among them, KDT08 and KDT21 which fall under same genus Dysidea, yet possess insignificant cytotoxicity against colorectal cancer cells. This research article provides a preliminary test for cytotoxicity activity of a wide range of marine sponges. Throughout this study, acquired results could provide useful information to determine the worthiness to further isolate nor purify the nature product from these sponges.

scholarly journals Onion Peel Extract Inhibits Cancer Cell Growth and Progression through the Roles of L1CAM, NF-κB, and Angiogenesis in HT-29 Colorectal Cancer Cells

2021 ◽  
Vol 26 (3) ◽  
pp. 330-337
Author(s):  
Tamonwan Uttarawichien ◽  
Wilunplus Khumsri ◽  
Prasit Suwannalert ◽  
Nathawut Sibmooh ◽  
Witchuda Payuhakrit
Keyword(s):  
Colorectal Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Cell Growth ◽  
Onion Peel ◽  
Colorectal Cancer Cells ◽  
Onion Peel Extract ◽  
Ht 29 ◽  
Peel Extract

scholarly journals Proteomic characterization of GSK3β knockout shows altered cell adhesion and metabolic pathway utilisation in colorectal cancer cells.

2021 ◽  
Author(s):  
E.H. Bowler-Barnett ◽  
F. D. Martinez-Garcia ◽  
M. Sherwood ◽  
S. Weston ◽  
Y. Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Adhesion ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Model ◽  
Cancer Cell Line ◽  
Glycogen Metabolism ◽  
Colorectal Cancer Cell ◽  
Colorectal Cancer Cell Line ◽  
Colorectal Cancer Cells

ABSTRACTGlycogen-specific kinase (GSK3β) is an integral regulator of the Wnt signalling pathway as well as many other diverse signalling pathways and processes. Dys-regulation of GSK3β is implicated in many different pathologies, including neurodegenerative disorders as well as many different tumour types. In the context of tumour development, GSK3β has been shown to play both oncogenic and tumour suppressor roles, depending upon tissue, signalling environment or disease progression. Although multiple substrates of the GSK3β kinase have been identified, the wider protein networks within which GSK3β participates are not well known, and the consequences of these interactions not well understood. In this study, LC-MS/MS expression analysis was performed using knockout GSK3β colorectal cancer cells and isogenic controls in colorectal cancer cell lines carrying dominant stabilizing mutations of β-Catenin. Consistent with the role GSK3β, we found that β-Catenin levels and canonical Wnt activity are unaffected by knockout of GSK3β and therefore use this knockout cell model to identify other processes in which GSK3β is implicated. Quantitative proteomic analysis revealed perturbation of proteins involved in cell-cell adhesion, and we characterize the phenotype and altered proteomic profiles associated with this. We also characterize the perturbation of metabolic pathways resulting from GSK3β knockout and identify defects in glycogen metabolism. In summary, using a precision colorectal cancer cell-line knockout model with constitutively activated β-Catenin we are able to identify several of the diverse pathways and processes associated with GSK3β function.

A Comparison of the Anti-Cancer Effects of Free and PLGA-PAA Encapsulated Hydroxytyrosol on the HT-29 Colorectal Cancer Cell Line

2021 ◽  
Vol 21 ◽  
Author(s):  
Nasrin S. Sani ◽  
Habib Onsori ◽  
Somayeh Akrami ◽  
Mohammad Rahmati
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Colorectal Cancer Cell ◽  
Colorectal Cancer Cell Line ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
Colorectal Cancer Cells

Background: Hydroxytyrosol is one of the phenolic compounds of olive oil and can induce anti-cancer effects on the colorectal cancer cells. Objective: The aim of the present study was to evaluate the free hydroxytyrosol and nano-capsulated hydroxytyrosol effects on the cell cycle arrest in HT-29 colorectal cancer cell line. Methods: The nano-capsulated hydroxytyrosol was synthesized in poly lactide-co-glycolide-co-polyacrylic acid (PLGA-PAA) copolymer. MTT assay was performed to evaluate the anti- proliferative and anti-tumor effects of the free hydroxytyrosol and nano-capsulated hydroxytyrosol. Finally, the relative expression of CDKN1A, CDKN1B and CCND1 genes was evaluated in the control and treated colorectal cancer cells by using Real-Time PCR. Results: The obtained results from the MTT assay showed that the cytotoxic effects of the nano-capsulated hydroxytyrosol on the colorectal cancer cell line (IC50= 6PPM) was significantly more than free hydroxytyrosol (IC50= 12PPM) after 72h. Also, nano-capsulated hydroxytyrosol showed more significant effects on the up-regulation of CDKN1A and CDKN1B genes, and down-regulation of the CCND1 gene in the colorectal cancer cells. Conclusion: In conclusion, the present study showed that the hydroxytyrosol led to die the colorectal cancer cell through the cell cycle arrest. Also, the PLGA-PAA copolymer dramatically caused to increase the cytotoxic effects of the hydroxytyrosol on the colorectal cancer cells.

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