Clinicopathological significance and angiogenic role of the constitutive phosphorylation of the FOXO1 transcription factor in colorectal cancer

AbstractCircular RNAs (circRNAs) have been reported to play crucial roles in the progression of various cancers, including colorectal cancer (CRC). SP1 (Sp1 transcription factor) is a well-recognized oncogene in CRC and is deemed to trigger the Wnt/β-catenin pathway. The present study was designed to investigate the role of circRNAs which shared the same pre-mRNA with SP1 in CRC cells. We identified that hsa_circ_0026628 (circ_0026628), a circular RNA that originated from SP1 pre-mRNA, was upregulated in CRC cells. Sanger sequencing and agarose gel electrophoresis verified the circular characteristic of circ_0026628. Functional assays including CCK-8, colony formation, transwell, immunofluorescence staining, and sphere formation assay revealed the function of circ_0026628. RNA pull-down and mass spectrometry disclosed the proteins interacting with circ_0026628. Mechanistic assays including RIP, RNA pull-down, CoIP, ChIP, and luciferase reporter assays demonstrated the interplays between molecules. The results depicted that circ_0026628 functioned as a contributor to CRC cell proliferation, migration, EMT, and stemness. Mechanistically, circ_0026628 served as the endogenous sponge of miR-346 and FUS to elevate SP1 expression at the post-transcriptional level, thus strengthening the interaction between SP1 and β-catenin to activate the Wnt/β-catenin pathway. In turn, the downstream gene of Wnt/β-catenin signaling, SOX2 (SRY-box transcription factor 2), transcriptionally activated SP1 and therefore boosted circ_0026628 level. On the whole, SOX2-induced circ_0026628 sponged miR-346 and recruited FUS protein to augment SP1, triggering the downstream Wnt/β-catenin pathway to facilitate CRC progression.

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Empty Spiracles Homeobox 2 (EMX2) Inhibits the Invasion and Tumorigenesis in Colorectal Cancer Cells

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504016x14756640150695 ◽

2017 ◽

Vol 25 (4) ◽

pp. 537-544 ◽

Cited By ~ 4

Author(s):

Yan Zhang ◽

Gang Cao ◽

Qing-gong Yuan ◽

Jun-hui Li ◽

Wen-Bin Yang

Keyword(s):

Colorectal Cancer ◽

Transcription Factor ◽

Essential Role ◽

Migration And Invasion ◽

Human Colorectal Cancer ◽

Potential Therapeutic Target ◽

Colorectal Cancer Cells ◽

Proliferation In Vitro

Empty spiracles homeobox 2 (EMX2) is a homeodomain-containing transcription factor that plays an essential role in tumorigenesis. However, to the best of our knowledge, the role of EMX2 in human colorectal cancer (CRC) is still unclear. Thus, the aim of this study was to investigate the expression and role of EMX2 in CRC. Our results demonstrated that the expression of EMX2 was greatly decreased in CRC tissues and cell lines. Overexpression of EMX2 significantly inhibited the proliferation in vitro and CRC tumor growth in nude mice. In addition, EMX2 also inhibited the migration and invasion of CRC cells. Mechanically, overexpression of EMX2 downregulated the expression levels of β-catenin, cyclin D1, and c-Myc in CRC cells. Taken together, our study demonstrates that EMX2 inhibits proliferation and tumorigenesis through inactivation of the Wnt/β-catenin pathway in CRC cells. Therefore, EMX2 may be a potential therapeutic target for the treatment of CRC.

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DNA hypermethylation contributes to colorectal cancer metastasis by regulating the binding of CEBPB and TFCP2 to the CPEB1 promoter

Clinical Epigenetics ◽

10.1186/s13148-021-01071-z ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Keke Shao ◽

Weilin Pu ◽

Jianfeng Zhang ◽

Shicheng Guo ◽

Fei Qian ◽

...

Keyword(s):

Colorectal Cancer ◽

Transcription Factor ◽

Cell Lines ◽

Binding Protein ◽

Tumour Suppressor ◽

Tumour Suppressor Genes ◽

Suppressor Genes

Abstract Background Aberrant DNA methylation has been firmly established as a factor contributing to the pathogenesis of colorectal cancer (CRC) via its capacity to silence tumour suppressor genes. However, the methylation status of multiple tumour suppressor genes and their roles in promoting CRC metastasis are not well characterised. Methods We explored the methylation and expression profiles of CPEB1 (the gene encoding cytoplasmic polyadenylation element-binding protein 1), a candidate CRC tumour suppressor gene, using The Cancer Genome Atlas (TCGA) database and validated these results in both CRC cell lines and cells from Han Chinese CRC patients (n = 104). The functional role of CPEB1 in CRC was examined in experiments performed in vitro and in vivo. A candidate transcription factor capable of regulating CPEB1 expression was predicted in silico and validated by luciferase reporter, DNA pull-down, and electrophoretic mobility shift assays. Results Hypermethylation and decreased expression of CPEB1 in CRC tumour tissues were revealed by TCGA database. We also identified a significant inverse correlation (Pearson’s R = − 0.43, P < 0.001) between promoter methylation and CPEB1 expression. We validated these results in CRC samples and two CRC cell lines. We also demonstrated that up-regulation of CPEB1 resulted in significantly decreased tumour growth, migration, invasion, and tumorigenicity and promoted tumour cell apoptosis both in vitro and in vivo. We identified the transcription factors CCAAT enhancer-binding protein beta (CEBPB) and transcription factor CP2 (TFCP2) as critical regulators of CPEB1 expression. Hypermethylation of the CPEB1 promoter resulted in a simultaneous increase in the capacity for TFCP2 binding and a decreased likelihood of CEBPB binding, both of which led to diminished expression of CPEB1. Conclusions Our results identified a novel tumour-suppressive role of CPEB1 in CRC and found that hypermethylation of the CPEB1 promoter may lead to diminished expression due to decreased chromatin accessibility and transcription factor binding. Collectively, these results suggest a potential role for CPEB1 in the diagnosis and treatment of CRC.

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Sa2050 The Role of Transcription Factor GFI1 in Colorectal Cancer Progression and Metastasis

Gastroenterology ◽

10.1016/s0016-5085(16)31527-x ◽

2016 ◽

Vol 150 (4) ◽

pp. S439-S440

Author(s):

Min-Shan Chen ◽

Yuan-Hung Lo ◽

Xi Chen ◽

Christopher S. Williams ◽

Noah F. Shroyer

Keyword(s):

Colorectal Cancer ◽

Transcription Factor ◽

Cancer Progression ◽

Colorectal Cancer Progression

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Role of Oxidative Stress and Nrf2/KEAP1 Signaling in Colorectal Cancer: Mechanisms and Therapeutic Perspectives with Phytochemicals

Antioxidants ◽

10.3390/antiox10050743 ◽

2021 ◽

Vol 10 (5) ◽

pp. 743

Author(s):

Da-Young Lee ◽

Moon-Young Song ◽

Eun-Hee Kim

Keyword(s):

Oxidative Stress ◽

Colorectal Cancer ◽

Transcription Factor ◽

Cancer Progression ◽

Inflammatory Diseases ◽

Negative Regulator ◽

Related Factor ◽

Cancer Society ◽

Incidence And Mortality

Colorectal cancer still has a high incidence and mortality rate, according to a report from the American Cancer Society. Colorectal cancer has a high prevalence in patients with inflammatory bowel disease. Oxidative stress, including reactive oxygen species (ROS) and lipid peroxidation, has been known to cause inflammatory diseases and malignant disorders. In particular, the nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-related protein 1 (KEAP1) pathway is well known to protect cells from oxidative stress and inflammation. Nrf2 was first found in the homolog of the hematopoietic transcription factor p45 NF-E2, and the transcription factor Nrf2 is a member of the Cap ‘N’ Collar family. KEAP1 is well known as a negative regulator that rapidly degrades Nrf2 through the proteasome system. A range of evidence has shown that consumption of phytochemicals has a preventive or inhibitory effect on cancer progression or proliferation, depending on the stage of colorectal cancer. Therefore, the discovery of phytochemicals regulating the Nrf2/KEAP1 axis and verification of their efficacy have attracted scientific attention. In this review, we summarize the role of oxidative stress and the Nrf2/KEAP1 signaling pathway in colorectal cancer, and the possible utility of phytochemicals with respect to the regulation of the Nrf2/KEAP1 axis in colorectal cancer.

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The role of transcription factor caudal-related homeobox transcription factor 2 in colorectal cancer

Tzu Chi Medical Journal ◽

10.4103/tcmj.tcmj_49_20 ◽

2020 ◽

Vol 32 (4) ◽

pp. 305

Author(s):

Chin-Chia Wu ◽

Ta-Wen Hsu ◽

Chia-Chou Yeh ◽

Hsien-Bing Huang

Keyword(s):

Colorectal Cancer ◽

Transcription Factor ◽

Homeobox Transcription Factor

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The role of Snail1 transcription factor in colorectal cancer progression and metastasis

Współczesna Onkologia ◽

10.5114/wo.2014.42173 ◽

2015 ◽

Vol 4 ◽

pp. 265-270 ◽

Cited By ~ 6

Author(s):

Marlena Brzozowa ◽

Marek Michalski ◽

Grzegorz Wyrobiec ◽

Adam Piecuch ◽

Anna Dittfeld ◽

...

Keyword(s):

Colorectal Cancer ◽

Transcription Factor ◽

Cancer Progression ◽

Colorectal Cancer Progression

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Clinicopathological significance and prognostic role of tumor-infiltrating lymphocytes in colorectal cancer

The International Journal of Biological Markers ◽

10.1177/1724600818817320 ◽

2019 ◽

Vol 34 (2) ◽

pp. 132-138 ◽

Cited By ~ 9

Author(s):

Young San Ko ◽

Jung-Soo Pyo

Keyword(s):

Colorectal Cancer ◽

Immune Cells ◽

Tumor Infiltrating Lymphocytes ◽

Prognostic Role ◽

Significant Difference ◽

Clinicopathological Significance ◽

Cancer Tissues ◽

Infiltrating Lymphocytes ◽

The Impact

Purpose: This study aimed to elucidate the clinicopathological significance and prognostic role of tumor-infiltrating lymphocytes in colorectal cancer. Methods: The immunohistochemistry of CD3 and CD8 was performed on 265 human colorectal cancer tissues to investigate the tumor-infiltrating lymphocytes using Immunoscore. The correlation between Immunoscore and clinicopathological characteristics, including survival rates, was elucidated. In addition, the impact of tumor-infiltrating lymphocytes on programmed death-ligand 1 (PD-L1) protein expression was evaluated through immunohistochemistry. Results: Of the 265 colorectal cancer tissues, 40.8% had high Immunoscore, while 59.2% had low Immunoscore. A high Immunoscore was significantly correlated with favorable tumor behaviors, including lower rates of vascular, lymphatic, and perineural invasion; lymph node metastasis; and distant metastasis. PD-L1 expressions of tumor and immune cells were significantly higher in patients with high Immunoscore than in those with low Immunoscore. In addition, colorectal cancer tissues with high CD8-positive lymphocytes showed higher PD-L1 expressions of tumor and immune cells than colorectal cancer tissues with low CD8-positive lymphocytes. There was a significant correlation between high Immunoscore and better overall survival. However, there was no significant difference in survival rate according to PD-L1 expressions of tumor and immune cells in high and low Immunoscore subgroups. Conclusions: Taken together, our results showed that high tumor-infiltrating lymphocytes were significantly correlated with favorable tumor behaviors and better survival. In addition, there was a significant correlation between PD-L1 expression and tumor-infiltrating lymphocytes.

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