<i>Growth Factor–Independent 1</i> Is a Tumor Suppressor Gene in Colorectal Cancer

Chen, Min Shan; Lo, Yuan Hung; Chen, Xi; Williams, Christopher S.; Donnelly, Jessica M.; Criss, Zachary K.; Patel, Shreena; Butkus, Joann M.; Dubrulle, Julien; Finegold, Milton J.; Shroyer, Noah F.

doi:10.1158/1541-7786.mcr-18-0666

Cited by 42 publications

(28 citation statements)

References 51 publications

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“…A similar scenario is found in solid tissues such as lung, inner ear hair epithelium, nervous system, and intestinal epithelium, in which Gfi1 function depends on the tissue, again suggesting a dual role for this transcription factor [16]. Two recent studies reported Gfi1 downregulation in colorectal cancer suggesting a tumor suppressor role in this tissue [17,20]. Our data can be explained by proposing a similar role for Gfi1 in prostate and breast cancer.…”

Section: Discussionsupporting

confidence: 85%

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Epigenetic Regulation of Gfi1 in Endocrine-Related Cancers: A Role Regulating Tumor Growth

Ashour

Angulo

González-Corpas

et al. 2020

IJMS

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Prostate and breast cancer constitute the most common cancers among men and women worldwide. The aging population is one of the main risk factors for prostate and breast cancer development and accumulating studies link aging with epigenetic changes. Growth factor independence-1 (Gfi1) is a transcriptional repressor with an important role in human malignancies, including leukemia, colorectal carcinoma, and lung cancer, but its role in prostate and breast cancer is unknown. We have found that Gfi1 epigenetic silencing is a common event in prostate and breast cancer. Gfi1 re-expression in prostate and breast cancer cell lines displaying Gfi1 epigenetic silencing decreases cell proliferation, reduced colony formation density, and tumor growth in nude mice xenografts. In addition, we found that Gfi1 repress alpha 1-anti-trypsin (AAT) and alpha 1-anti-chymotrypsin (ACT) expression, two genes with important functions in cancer development, suggesting that Gfi1 silencing promotes tumor growth by increasing AAT and ACT expression in our system. Finally, Gfi1 epigenetic silencing could be a promising biomarker for prostate cancer progression because it is associated with shorter disease-free survival. In conclusion, our findings strongly indicate that Gfi1 epigenetic silencing in prostate and breast cancer could be a crucial step in the development of these two-well characterized endocrine related tumors.

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Section: Discussionsupporting

confidence: 85%

“…Tumor suppressor properties have been proposed for Gfi1 since its re-expression in cancer cell lines lacking Gfi1 function decreases cell proliferation [16,20]. We assessed the ability of Gfi1 to function as tumor suppressor gene in prostate and breast cancer cell lines.…”

Section: Gfi1 Re-expression Genes Decreases Cell and Tumor Growth Andmentioning

confidence: 99%

Epigenetic Regulation of Gfi1 in Endocrine-Related Cancers: A Role Regulating Tumor Growth

Ashour

Angulo

González-Corpas

et al. 2020

IJMS

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“…To investigate the underlying mechanism of SLC2A3 expression, we divided them into low-SLC2A3 expression group and high-SLC2A3 expression group based on SLC2A3 median expression level. Moreover, GSE17536(N = 177) and GSE17537 (N = 55) data (11)(12)(13)(14) were applied for further prognosis validation, which were from Gene Expression Omnibus (GEO) data (https://www.ncbi.nlm.nih.gov/geo/ query/acc.cgi?acc=GSE17536 and https://www.ncbi.nlm.nih. gov/geo/query/acc.cgi?acc=GSE17537).…”

Section: Data Miningmentioning

confidence: 99%

A Prognosis Marker SLC2A3 Correlates With EMT and Immune Signature in Colorectal Cancer

et al. 2021

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SLC2A3 is a membrane transporter that belongs to the solute carrier family, whose function includes transmembrane transport and glucose transmembrane transport activity. To clarify the expression and role of SLC2A3 in colorectal cancer (CRC), we analyzed the TCGA and GEO databases and found that SLC2A3 mRNA levels were significantly higher in CRC tissues than that in adjacent non-tumor tissues. Furthermore, high expression of SLC2A3 predicted poor overall survival and disease free survival for CRC patients. For validation, we collected 174 CRC samples and found that SLC2A3 expression was higher in CRC tissues than that in adjacent non-tumor colorectal mucosa tissues by immunohistochemistry staining. Further study showed that high expression of SLC2A3 was enriched in epithelial–mesenchymal transition (EMT) classical pathway, interferon-γ pathway by GSEA analysis enrichment, indicating that SLC2A3 may play a key role in the progression of CRC through EMT and immune response, which also has been validated by the global gene expression profiling of human CRC cell lines. The expression of SLC2A3 was positively correlated with CD4 and CD8+T cells by using TIMER and EPIC algorithm, respectively. SLC2A3 knockdown suppressed migration and inhibited the expression of Vimentin and MMP9 in CRC cell line SW480 and RKO. Meanwhile, PD-L1 expression was also significantly attenuated in SW480 and RKO cells transfected with SLC2A3 siRNA. The result suggests that SLC2A3 may be involved in the immune response of CRC by regulating PD-L1 immune checkpoint. In our series, SLC2A3 and PD-L1 positive expression was 74% (128/174) and 22% (39/174) of CRC, respectively. SLC2A3 expression was significantly associated with perineural invasion in CRC patients. In conclusion, SLC2A3 may play an important role in progression of CRC by regulating EMT and PD-L1 mediated immune responses.

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“…GFI1 is a kind of DNA binding zinc finger protein and it can mediate transcriptional repression through recruiting histone-modifying enzymes to its targets (31). Downregulation of GFI1 can promote inflammation-linked metastasis of colorectal cancer, and it is a tumor suppressor gene (32,33).Currently, we proved that GFI1 was down-regulated in HCC tissues and cells. Meanwhile, GFI1 interacted with the LINC00675 promoter via the three binding sites.…”

Section: Discussionmentioning

confidence: 88%

GFI1-Mediated Upregulation of LINC00675 as a ceRNA Restrains Hepatocellular Carcinoma Metastasis by Sponging miR-942-5p

Zhang

et al. 2021

Front. Oncol.

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Hepatocellular carcinoma (HCC) is a common malignant liver tumor worldwide. Tumor recurrence and metastasis contribute to the bad clinical outcome of HCC patients. Substantial studies have displayed lncRNAs modulate various tumorigenic processes of many cancers. Our current work was aimed to investigate the function of LINC00675 in HCC and to recognize the potential interactions between lncRNAs and microRNAs. GFI1 can exhibit a significant role in the progression of human malignant tumors. Firstly, GFI1 was identified using real-time PCR in HCC tissues and cells. In this work, we indicated GFI1 was remarkably reduced in HCC tissues and cells. Meanwhile, GFI1 specifically interacted with the promoter of LINC00675. Up-regulation of LINC00675 obviously repressed the migration and invasion capacity of SMCC-7721 and QGY-7703 cells in vitro. Moreover, decrease of LINC00675 competitively bound to miR-942-5p that contributed to the miRNA-mediated degradation of GFI1, thus facilitated HCC metastasis. The ceRNA function of LINC00675 in HCC cells was assessed and confirmed using RNA immunoprecipitation assay and RNA pull-down assays in our work. Additionally, we proved overexpression of miR-942-5p promoted HCC progression, which was reversed by the up-regulation of GFI1. In summary, LINC00675 might act as a prognostic marker for HCC, which can inhibit HCC development via regulating miR-942-5p and GFI1.

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Growth Factor–Independent 1 Is a Tumor Suppressor Gene in Colorectal Cancer

Cited by 42 publications

References 51 publications

Epigenetic Regulation of Gfi1 in Endocrine-Related Cancers: A Role Regulating Tumor Growth

Epigenetic Regulation of Gfi1 in Endocrine-Related Cancers: A Role Regulating Tumor Growth

A Prognosis Marker SLC2A3 Correlates With EMT and Immune Signature in Colorectal Cancer

GFI1-Mediated Upregulation of LINC00675 as a ceRNA Restrains Hepatocellular Carcinoma Metastasis by Sponging miR-942-5p

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