Transcription Factors: The Fulcrum Between Cell Development and Carcinogenesis

Islam, Zeyaul; Ali, Ameena M; Belič, Aleš; Eldaw, Mohamed; Decock, Julie; Kolatkar, Prasanna R.

doi:10.3389/fonc.2021.681377

Cited by 32 publications

(16 citation statements)

References 261 publications

(254 reference statements)

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“…Apart from their role in human development, AP-2 transcription factors are also known to influence carcinogenesis; as such, they have prognostic value for cancer patients 11 , 12 . Once regarded as “undruggable” DNA-binding proteins, transcription factors are now the object of studies examining selective modulators of their activity 8 , 13 , 14 . Among these factors, AP-2 is of particular significance since one of the members from this family, AP-2δ (encoded by the TFAP2D gene), is one of less than three hundred candidate transcription factors suitable for studies focused on examining selective modulators of transcription factor activity 15 .…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of AP-2α/γ targets as cancer therapeutics

Kołat

Kałuzińska

Płuciennik

2022

Sci Rep

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Identifying genes with prognostic importance could improve cancer treatment. An increasing number of reports suggest the existence of successful strategies based on seemingly “untargetable” transcription factors. In addition to embryogenesis, AP-2 transcription factors are known to play crucial roles in cancer development. Members of this family can be used as prognostic factors in oncological patients, and AP-2α/γ transcription factors were previously investigated in our pan-cancer comparative study using their target genes. The present study investigates tumors that were previously found similar with an emphasis on the possible role of AP-2 factors in specific cancer types. The RData workspace was loaded back to R environment and 3D trajectories were built via Monocle3. The genes that met the requirement of specificity were listed using top_markers(), separately for mutual and unique targets. Furthermore, the candidate genes had to meet the following requirements: correlation with AP-2 factor (through Correlation AnalyzeR) and validated prognostic importance (using GEPIA2 and subsequently KM-plotter or LOGpc). Eventually, the ROC analysis was applied to confirm their predictive value; co-dependence of expression was visualized via BoxPlotR. Some similar tumors were differentiated by AP-2α/γ targets with prognostic value. Requirements were met by only fifteen genes (EMX2, COL7A1, GRIA1, KRT1, KRT14, SLC12A5, SEZ6L, PTPRN, SCG5, DPP6, NTSR1, ARX, COL4A3, PPEF1 and TMEM59L); of these, the last four were excluded based on ROC curves. All the above genes were confronted with the literature, with an emphasis on the possible role played by AP-2 factors in specific cancers. Following ROC analysis, the genes were verified using immunohistochemistry data and progression-related signatures. Staining differences were observed, as well as co-dependence on the expression of e.g. CTNNB1, ERBB2, KRAS, SMAD4, EGFR or MKI67. In conclusion, prognostic value of targets suggested AP-2α/γ as candidates for novel cancer treatment. It was also revealed that AP-2 targets are related to tumor progression and that some mutual target genes could be inversely regulated.

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Section: Discussionmentioning

confidence: 99%

Prognostic significance of AP-2α/γ targets as cancer therapeutics

Kołat

Kałuzińska

Płuciennik

2022

Sci Rep

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“…Transcription factors (TFs) are proteins in eukaryotic cells that assist in and regulate the transcription of mRNAs by RNA polymerase. Some core TFs are proteins encoded by oncogenes or tumor suppressor genes and are directly involved in target gene transcription during cell proliferation by binding to the cis-acting elements of the target genes ( 122 ). The following section provides a brief overview of some of the most important lncRNAs that act as TFs in CRCSCs ( Table 1 , Figure 2 ).…”

Section: Research Progress On Lncrnas That Participate In the Regulat...mentioning

confidence: 99%

LncRNAs, the Molecules Involved in Communications With Colorectal Cancer Stem Cells

et al. 2022

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Colorectal cancer stem cells (CRCSCs) can actively self-renew, as well as having multidirectional differentiation and tumor regeneration abilities. Because the high functional activities of CRCSCs are associated with low cure rates in patients with colorectal cancer, efforts have sought to determine the function and regulatory mechanisms of CRCSCs. To date, however, the potential regulatory mechanisms of CRCSCs remain incompletely understood. Many non-coding genes are involved in tumor invasion and spread through their regulation of CRCSCs, with long non-coding RNAs (lncRNAs) being important non-coding RNAs. LncRNAs may be involved in the colorectal cancer development and drug resistance through their regulation of CRCSCs. This review systematically evaluates the latest research on the ability of lncRNAs to regulate CRCSC signaling pathways and the involvement of these lncRNAs in colorectal cancer promotion and suppression. The regulatory network of lncRNAs in the CRCSC signaling pathway has been determined. Further analysis of the potential clinical applications of lncRNAs as novel clinical diagnostic and prognostic biomarkers and therapeutic targets for colorectal cancer may provide new ideas and protocols for the prevention and treatment of colorectal cancer.

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“…Stemness and differentiation are, ultimately, under the precise control of gene expression programs ( Takahashi and Yamanaka, 2016 ; Almeida et al, 2021 ; Islam et al, 2021 ). The initiation and maintenance of specific gene expression patterns is achieved by specific combinations of transcriptional regulators, subjected to a variety of post translational modifications controlling their activity, molecular interactions, sub cellular localization and half-life.…”

Section: Ups and The Regulation Of Satellite Cell Functionmentioning

confidence: 99%

The Gentle Side of the UPS: Ubiquitin-Proteasome System and the Regulation of the Myogenic Program

Olguín

2022

Front. Cell Dev. Biol.

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In recent years, the ubiquitin-proteasome system (UPS) has emerged as an important regulator of stem cell function. Here we review recent findings indicating that UPS also plays critical roles in the biology of satellite cells, the muscle stem cell responsible for its maintenance and regeneration. While we focus our attention on the control of key transcriptional regulators of satellite cell function, we briefly discuss early studies suggesting the UPS participates more broadly in the regulation of satellite cell stemness and regenerative capacity.

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Transcription Factors: The Fulcrum Between Cell Development and Carcinogenesis

Cited by 32 publications

References 261 publications

Prognostic significance of AP-2α/γ targets as cancer therapeutics

Prognostic significance of AP-2α/γ targets as cancer therapeutics

LncRNAs, the Molecules Involved in Communications With Colorectal Cancer Stem Cells

The Gentle Side of the UPS: Ubiquitin-Proteasome System and the Regulation of the Myogenic Program

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