scholarly journals Identification of histone methyltransferase NSD2 as an important oncogenic gene in colorectal cancer

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Li-hao Zhao ◽  
Quan Li ◽  
Zhi-Jun Huang ◽  
Mi-Xue Sun ◽  
Jing-jing Lu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Histone Methyltransferase ◽  
Migration And Invasion ◽  
Colon Cancer Cells ◽  
Akt Activation ◽  
Primary Colon Cancer ◽  
Primary Colon

AbstractColorectal cancer (CRC) is the second common cause of cancer-related human mortalities. Dysregulation of histone 3 (H3) methylation could lead to transcriptional activation of multiple oncogenes, which is closely associated with CRC tumorigenesis and progression. Nuclear receptor-binding SET Domain protein 2 (NSD2) is a key histone methyltransferase catalyzing histone H3 lysine 36 dimethylation (H3K36me2). Its expression, the potential functions, and molecular mechanisms in CRC are studied here. Gene Expression Profiling Interactive Analysis (GEPIA) bioinformatics results showed that the NSD2 mRNA expression is elevated in both colon cancers and rectal cancers. Furthermore, NSD2 mRNA and protein expression levels in local colon cancer tissues are significantly higher than those in matched surrounding normal tissues. In primary human colon cancer cells and established CRC cell lines, shRNA-induced silencing or CRISPR/Cas9-induced knockout of NSD2 inhibited cell viability, proliferation, cell cycle progression, migration, and invasion. Furthermore, NSD2 shRNA or knockout induced mitochondrial depolarization, DNA damage, and apoptosis in the primary and established CRC cells. Contrarily, ectopic NSD2 overexpression in primary colon cancer cells further enhanced cell proliferation, migration, and invasion. H3K36me2, expressions of multiple oncogenes (ADAM9, EGFR, Sox2, Bcl-2, SYK, and MET) and Akt activation were significantly decreased after NSD2 silencing or knockout in primary colon cancer cells. Their levels were however increased after ectopic NSD2 overexpression. A catalytic inactive NSD2 (Y1179A) also inhibited H3K36me2, multiple oncogenes expression, and Akt activation, as well as cell proliferation and migration in primary colon cancer cells. In vivo, intratumoral injection of adeno-associated virus (AAV)-packed NSD2 shRNA largely inhibited primary colon cancer cell xenograft growth in nude mice. Together, NSD2 exerted oncogenic functions in CRC and could be a promising therapeutic target.

scholarly journals Cancer Preventive Effect of a Novel High Phenolic Sorghum Bran on Human Colon Cancer Cells (P05-008-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Seong-Ho Lee ◽  
Jihye Lee ◽  
Thomas Herald ◽  
Sarah Cox ◽  
Leela Noronha ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Citric Acid ◽  
Cancer Cells ◽  
Human Colon ◽  
Migration And Invasion ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Sorghum Bran ◽  
Human Colon Cancer Cells

Abstract Objectives Colon cancer is one of leading causes of cancer mortality worldwide. Sorghum is the fifth most largely cultivated crop for human diet in the world. Most sorghum varieties contain high content of phenolic compounds. The objective of the current study is to evaluate the anti-cancer properties of a novel high phenolic sorghum bran extract prepared under 70% ethanol with 5% citric acid solvent. Methods High phenolic sorghum, accession number PI570481, was grown in Puerto Vallarta, Mexico winter nursery during the 2018 and high phenolic sorghum bran extract was prepared using 70% ethanol with 5% citric acid solvent at room temperature for 2 hours. Human colon cancer cell lines (HCT15, SW480, HCT116 and HT-29) were treated with different doses of high phenolic sorghum bran extract. Cell proliferation and apoptosis was measured using MTS assay and Alexa Fluor 488 Annexin V/Dead Cell Apoptosis system, respectively. Distribution of cell cycle was measured Texas Red channel using BD LSRFortessa system. Cell migration and invasion was measured using wound healing assay and Matrigel, respectively. The luciferase activity of reporter genes was measured using a dual-luciferase assay and Western blot was performed to measure expression of cancer phenotype-associated proteins. Results Cell proliferation was inhibited and apoptosis was induced in the human colon cancer cells treated with high phenolic sorghum bran extract in a dose-dependent manner. High phenolic sorghum bran extract led to S phage arrest. Cell migration and invasion was also repressed in the human colon cancer cells treated with high phenolic sorghum bran extract. The change of cancer phenotypes was associated with up- or down-regulation of regulatory genes. Conclusions The present study expands our understanding on the potential use of high phenolic sorghum bran for prevention of human colon cancer. Funding Sources Cooperative Agreement grant from USDA-ARS to S-HL.

scholarly journals Atypical role of sprouty in colorectal cancer: sprouty repression inhibits epithelial–mesenchymal transition

Oncogene ◽  
2015 ◽  
Vol 35 (24) ◽  
pp. 3151-3162 ◽  
Author(s):  
Q Zhang ◽  
T Wei ◽  
K Shim ◽  
K Wright ◽  
K Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Colon Cancer Cells ◽  
Mesenchymal Transition ◽  
E Cadherin

Abstract Sprouty (SPRY) appears to act as a tumor suppressor in cancer, whereas we demonstrated that SPRY2 functions as a putative oncogene in colorectal cancer (CRC) (Oncogene, 2010, 29: 5241–5253). We investigated the mechanisms by which SPRY regulates epithelial–mesenchymal transition (EMT) in CRC. SPRY1 and SPRY2 mRNA transcripts were significantly upregulated in human CRC. Suppression of SPRY2 repressed AKT2 and EMT-inducing transcription factors and significantly increased E-cadherin expression. Concurrent downregulation of SPRY1 and SPRY2 also increased E-cadherin and suppressed mesenchymal markers in colon cancer cells. An inverse expression pattern between AKT2 and E-cadherin was established in a human CRC tissue microarray. SPRY2 negatively regulated miR-194-5p that interacts with AKT2 3′ untranslated region. Mir-194 mimics increased E-cadherin expression and suppressed cancer cell migration and invasion. By confocal microscopy, we demonstrated redistribution of E-cadherin to plasma membrane in colon cancer cells transfected with miR-194. Spry1 −/− and Spry2 −/− double mutant mouse embryonic fibroblasts exhibited decreased cell migration while acquiring several epithelial markers. In CRC, SPRY drive EMT and may serve as a biomarker of poor prognosis.

scholarly journals RAB27A Promotes the Proliferation and Invasion of Colorectal Cancer Cells

2022 ◽  
Author(s):  
Qingyan Li ◽  
Huixia Zhao ◽  
Weiwei Dong ◽  
Na Guan ◽  
Yanyan Hu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Ectopic Expression ◽  
Small Gtpases ◽  
Colon Cancer Cell ◽  
Colon Cancer Cells ◽  
Exact Function

Abstract Colorectal cancer (CRC) is the most commonly diagnosed form of cancer worldwide. Though significant advances in prevention and diagnosis, CRC is still one of the leading causes of cancer-related mortality globally. RAB27A, the member of RAB27 family of small GTPases, is the critical protein for intracellular secretion and was reported to promote tumor progression. However, it is controversial for the role of RAB27A in CRC progression, so we explored the exact function of RAB27A in CRC development in this study. Based on the stable colon cancer cell lines of RAB27A knockdown and ectopic expression, we found that RAB27A knockdown inhibited SW480 colon cancer cell proliferation and clone formation, whereas ectopic expression of RAB27A in RKO colon cancer cells facilitated cell proliferation and clone formation, indicating that RAB27A is critical for colon cancer cell growth. In addition, our data demonstrated that the migration and invasion of colon cancer cells were suppressed by RAB27A knockdown, but promoted by RAB27A ectopic expression. Therefore, RAB27A was identified as an onco-protein in mediating CRC development, which may be a valuable prognostic indicator and potential therapeutic target for CRC.

Xanthohumol reduces inflammation and cell metabolism in HT29 primary colon cancer cells

2021 ◽  
pp. 1-9
Author(s):  
Margalida Torrens-Mas ◽  
Marina Alorda-Clara ◽  
Maria Martínez-Vigara ◽  
Pilar Roca ◽  
Jorge Sastre-Serra ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Metabolism ◽  
Colon Cancer Cells ◽  
Primary Colon Cancer ◽  
Primary Colon

Abstract 252: Molecular characterization of cancer stem cells isolated from primary colon cancer cells.

2013 ◽  
Author(s):  
Martin Lange ◽  
Dirk Schumacher ◽  
Thomas Hauling ◽  
Christian Regenbrecht ◽  
Oliver Politz ◽  
...  
Keyword(s):  
Stem Cells ◽  
Colon Cancer ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Molecular Characterization ◽  
Colon Cancer Cells ◽  
Primary Colon Cancer ◽  
Primary Colon

scholarly journals HMGB1 released from GSDME-mediated pyroptotic epithelial cells participates in the tumorigenesis of colitis-associated colorectal cancer through the ERK1/2 pathway

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Gao Tan ◽  
Chongyang Huang ◽  
Jiaye Chen ◽  
Fachao Zhi
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Neutralizing Antibodies ◽  
Specific Inhibitor ◽  
Nuclear Antigen ◽  
Mucosal Inflammation ◽  
Colon Cancer Cells

Abstract Background Pyroptosis is a form of proinflammatory gasdermin-mediated programmed cell death. Abnormal mucosal inflammation in the intestine is a critical risk factor for colitis-associated colorectal cancer (CAC). However, it is unknown whether pyroptosis participates in the development of CAC. Methods To investigate the role of gasdermin E (GSDME)-mediated pyroptosis in the development of CAC, Gsdme−/− mice and their wild-type (WT) littermate controls were challenged with azoxymethane (AOM) and dextran sodium sulfate (DSS) to induce a CAC model. Neutralizing antibodies against high-mobility group box protein 1 (HMGB1) were used to determine the role of HMGB1 in CAC. To identify the role of ERK1/2 in HMGB1-induced colon cancer cell proliferation, we performed western blotting and CCK8 assays using the ERK1/2-specific inhibitor U0126 in CT26 colon cancer cells. Results In the CAC model, Gsdme−/− mice exhibited reduced weight loss and colon shortening, attenuated rectal prolapse, and reduced tumor numbers and sizes compared to WT littermates. Furthermore, treatment with neutralizing anti-HMGB1 antibodies decreased the numbers and sizes of tumors, ERK1/2 activation and proliferating cell nuclear antigen (PCNA) expression in AOM/DSS-challenged WT mice. In addition, our in vitro experiments demonstrated that HMGB1 induced proliferation and PCNA expression in CT26 colon cancer cells through the ERK1/2 pathway. Conclusion GSDME-mediated pyroptosis promotes the development of CAC by releasing HMGB1, which induces tumor cell proliferation and PCNA expression through the ERK1/2 pathway. This finding reveals a previously unrecognized link between pyroptosis and CAC tumorigenesis and offers new insight into CAC pathogenesis.

scholarly journals ID: 1029 Effects of carnosine on regulation of migration and invasion in human colorectal cancer cells

2017 ◽  
Vol 4 (S) ◽  
pp. 104 ◽  
Author(s):  
Po-Yu Lai ◽  
Shu-Chen Hsieh ◽  
Chih-Chung Wu ◽  
Shu-Ling Hsieh
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Human Colon ◽  
Migration And Invasion ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Hct 116 ◽  
Hct 116 Cells ◽  
Human Colon Cancer Cells

Colorectal cancer is the third most commonly diagnosed cancer in the word. Carnosine is an endogenous dipeptide found in vertebrate skeletal muscles. It is known to have anti-fatigue, antioxidative, antihypertensive, antidiabetic, and cancer inhibiting effects. However, little research has been done regarding its influence on the metastasis of colon cancer. This study cultivated HCT-116 human colon cancer cells as a test model in order to investigate the impact of carnosine on the migration and invasion of human colon cancer cells. The results showed that 48-hour treatments of HCT-116 cells with 0.5, 1, or 5 mM carnosine each significantly inhibited the migration ability of the cells (P < 0.05). The 48-hour treatments with 0.5, 1, or 5 mM carnosine were also found to significantly reduce MMP-9 activity (P < 0.05), but not MMP-2 expression. Furthermore, when HCT-116 cells treated with 1 or 5 mM carnosine, invasion ability are significantly decreased and significantly increased E-cadherin expression (P < 0.05). On the other hand, the protein of TIMP-1, an inhibitor of MMP-9, is signification increased after 1 or 5 mM carnosine treatment (P<0.05). In addition, the u-PA protein level are significantly decreased after carnosine treatment. The results indicate that carnosine can regulate the migration and invasion by regulating MMPs and its regulator molecular expression in HCT-116 cells.

scholarly journals Long Noncoding RNA LINC01207 Promotes Colon Cancer Cell Proliferation and Invasion by Regulating miR-3125/TRIM22 Axis

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Ronghong Liu ◽  
Wenzeng Zhao ◽  
Haigang Wang ◽  
Jianbing Wang
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Noncoding Rna ◽  
Colon Cancer Cell ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation ◽  
Colon Cancer Cells ◽  
Proliferation And Invasion

Increasing study has validated that long noncoding RNAs (lncRNAs) are involved in the growth and metastasis of colon cancer. LINC01207 has been reported to play vital roles in certain types of cancer, while the precise function of LINC01207 in the progression of colon cancer remains unclear. The objective of this study was to investigate the effect of LINC01207 on the growth and metastasis of colon cancer cells and to explore the underlying mechanism. We found that the expression of LINC01207 was significantly upregulated in colon adenocarcinoma tissues compared with normal tissues by the GEPIA database. Notably, silencing of LINC01207 significantly suppressed the proliferation, migration, and invasion abilities of SW480 and HT-29 cells. Mechanistically, our data demonstrated that LINC01207 could sponge miR-3125 in colon cancer cells. Moreover, miR-3125 could directly target TRIM22 and negatively regulate its expression. Rescue assays revealed that miR-3125 inhibitor or TRIM22 overexpression significantly reversed the repressive role of LINC01207 knockdown in colon cancer cell proliferation and invasion. In conclusion, LINC01207 exerts an oncogenic role in the progression of colon cancer by absorbing miR-3125 to modulating TRIM22 expression.

Response of Primary Colon Cancer Cells in Hybrid Spheroids to 5-Fluorouracil

1993 ◽  
Vol 11 (3) ◽  
pp. 291-298 ◽  
Author(s):  
Bozidar Djordjevic ◽  
Christopher S. Lange ◽  
Ronald R. Allison ◽  
Marvin Rotman
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Colon Cancer Cells ◽  
Primary Colon Cancer ◽  
Primary Colon
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