Transcription factors specificity protein and nuclear receptor 4A1 in pancreatic cancer

Safe, Stephen; Shrestha, Rupesh; Mohankumar, Kumaravel; Howard, Marcell; Hedrick, Erik; Abdelrahim, Maen

doi:10.3748/wjg.v27.i38.6387

Cited by 7 publications

(4 citation statements)

References 78 publications

(71 reference statements)

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“…In addition to being a target gene of microRNA, FOXF2 is upregulated by specificity protein 1 (SP1), myc-associated zinc-finger protein (MAZ), TGF-β and MCM3AP-AS1 (35)(36)(37)(38). Safe, Shrestha, Mohankumar, Howard, Hedrick and Abdelrahim (39) found that SP1 accelerates cell proliferation and migration of PC cells. MAZ is reported to promote invasiveness of PC cells (40).…”

Section: Discussionmentioning

confidence: 99%

Transcription factor FOXF2 promotes the development and progression of pancreatic cancer by targeting MSI2

Zhong,

Ma,

Sun

et al. 2024

Oncol Rep

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Pancreatic cancer (PC) is a malignant tumor possessing high mortality. The role of transcription factor Forkhead Box F2 (FOXF2) in PC remains unverified. The current study investigated the roles of FOXF2 in developing PC in vitro and in vivo. A xenograft tumor model was constructed with nude mice injected using FOXF2-overexpressing PC cells or FOXF2-silenced PC cells. High FOXF2 expression significantly enhanced the proliferation ability of PC cells in vitro and pancreatic tumor growth in vivo.The cell cycle analysis indicated that transition of G1-S phase was promoted by FOXF2. The cell cycle-associated proteins cyclin D1, CDK2, phosphorylated (p)-CDK2 and p-RB were upregulated in the FOXF2-overexpressing cells and downregulated in the cells with FOXF2 knockdown. Flow cytometric analysis and Hoechst staining showed that the percentage of apoptotic cells was significantly increased after FOXF2 was silenced. FOXF2 knockdown promoted expression of pro-apoptotic proteins (Bad, Bax and cleaved caspase-3) while suppressing the anti-apoptotic proteins (Bcl-2 and Bcl-xl) at the protein level. FOXF2 improved the migration and invasion of PC cells in vitro. Moreover, luciferase and chromatin immunoprecipitation assays revealed that FOXF2 binds to the MSI2 promoter, promoting its transcriptional expression. FOXF2 knockdown inhibited the MSI2 protein translation while enhancing the translation of NUMB protein, suppressing PC development in vivo. MSI2 silencing reversed the promotive effect mediated by FOXF2 on cell proliferation. These results demonstrated that FOXF2 is essential in PC progression, and the potential mechanism includes regulating MSI2 transcription.

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Section: Discussionmentioning

confidence: 99%

Transcription factor FOXF2 promotes the development and progression of pancreatic cancer by targeting MSI2

Zhong,

Ma,

Sun

et al. 2024

Oncol Rep

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“…TF is important regulators of intrinsic life processes within cells, possess DNA-binding domains and initiate transcription of genes [ 30 ]. Over the years, a large amount of data from different laboratories has shown that TFs are involved in progression of cancer [ 31 – 33 ]. For instance, FoxO1 promotes glioma cell proliferation by acting as a transcriptional activator of RFC2 [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

RFC2 promotes aerobic glycolysis and progression of colorectal cancer

Lou,

Zhang

2023

BMC Gastroenterol

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Background Replication factor C subunit 2 (RFC2) participates in the growth and metastasis of various malignancies. Our study investigated the roles of RFC2 in colorectal cancer (CRC). Results RFC2 expression was upregulated in CRC tissues and cells. High RFC2 expression was associated with poor prognosis. Knockdown RFC2 inhibited proliferation, induced apoptosis, and suppressed migration and invasion of CRC cells. CREB5 was a transcription factor of RFC2, and CREB5 knockdown suppressed RFC2 expression. Furthermore, RFC2 promoted aerobic glycolysis and MET/PI3K/AKT/mTOR pathway. Conclusion RFC2 promoted the progression of CRC cells via activating aerobic glycolysis and the MET/PI3K/AKT/mTOR pathway.

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“…These TFs might be important factors in the pathogenesis of RF. While Sp2, Sp3, and Sp4 were associated with cell proliferation, survival, migration, and invasion and highly expressed in tumors ( Zhao et al, 2014 ; Kim et al, 2017 ; Safe et al, 2021 ), their roles in fibrosis have yet to be reported. Whether and how these TFs participate in the pathogenesis of RF remain to be further studied.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analyses of the microRNA–messenger RNA–transcription factor regulatory network in mouse and human renal fibrosis

Deng

Huang

2022

Front. Genet.

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Objective: The aim of this study was to construct a microRNA (miRNA)–messenger RNA (mRNA)–transcription factor (TF) regulatory network and explore underlying molecular mechanisms, effective biomarkers, and drugs in renal fibrosis (RF).Methods: A total of six datasets were downloaded from Gene Expression Omnibus. “Limma” and “DESeq2” packages in R software and GEO2R were applied to identify the differentially expressed miRNAs and mRNAs (DEmiRNAs and DEmRNAs, respectively). The determination and verification of DEmiRNAs and DEmRNAs were performed through the integrated analysis of datasets from five mouse 7 days of unilateral ureteral obstruction datasets and one human chronic kidney disease dataset and the Human Protein Atlas (http://www.proteinatlas.org). Target mRNAs of DEmiRNAs and TFs were predicted by prediction databases and the iRegulon plugin in Cytoscape, respectively. A protein–protein interaction network was constructed using STRING, Cytoscape v3.9.1, and CytoNCA. Functional enrichment analysis was performed by DIANA-miRPath v3.0 and R package “clusterProfiler.” A miRNA–mRNA–TF network was established using Cytoscape. Receiver operating characteristic (ROC) curve analysis was used to examine the diagnostic value of the key hub genes. Finally, the Comparative Toxicogenomics Database and Drug-Gene Interaction database were applied to identify potential drugs.Results: Here, 4 DEmiRNAs and 11 hub genes were determined and confirmed in five mouse datasets, of which Bckdha and Vegfa were further verified in one human dataset and HPA, respectively. Moreover, Bckdha and Vegfa were also predicted by miR-125a-3p and miR-199a-5p, respectively, in humans as in mice. The sequences of miR-125a-3p and miR-199a-5p in mice were identical to those in humans. A total of 6 TFs were predicted to regulate Bckdha and Vegfa across mice and humans; then, a miRNA–mRNA–TF regulatory network was built. Subsequently, ROC curve analysis showed that the area under the curve value of Vegfa was 0.825 (p = 0.002). Finally, enalapril was identified to target Vegfa for RF therapy.Conclusion: Pax2, Pax5, Sp1, Sp2, Sp3, and Sp4 together with Bckdha-dependent miR-125a-3p/Vegfa-dependent miR-199a-5p formed a co-regulatory network enabling Bckdha/Vegfa to be tightly controlled in the underlying pathogenesis of RF across mice and humans. Vegfa could act as a potential novel diagnostic marker and might be targeted by enalapril for RF therapy.

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Transcription factors specificity protein and nuclear receptor 4A1 in pancreatic cancer

Cited by 7 publications

References 78 publications

Transcription factor FOXF2 promotes the development and progression of pancreatic cancer by targeting MSI2

Transcription factor FOXF2 promotes the development and progression of pancreatic cancer by targeting MSI2

RFC2 promotes aerobic glycolysis and progression of colorectal cancer

Comprehensive analyses of the microRNA–messenger RNA–transcription factor regulatory network in mouse and human renal fibrosis

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