The roles and regulation of the KLF5 transcription factor in cancers

Luo, Yao; Chen, Ceshi

doi:10.1111/cas.14910

Cited by 74 publications

(53 citation statements)

References 202 publications

(824 reference statements)

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“…These are essential for development, differentiation, and homeostasis 39,40 , suggesting the importance of these TFs in SWF and F1 stages. In contrast, POF-specific peaks in GCs are enriched in motifs corresponding to TFs involved in cytotoxicity and apoptosis induction [41][42][43] , including KLF5, PITX1, and OTX1 (Supplementary Fig. 6d).…”

Section: Resultsmentioning

confidence: 99%

Dynamic transcriptome and chromatin architecture in granulosa cells during chicken folliculogenesis

Ning

Zhang

et al. 2022

Nat Commun

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Folliculogenesis is a complex biological process involving a central oocyte and its surrounding somatic cells. Three-dimensional chromatin architecture is an important transcription regulator; however, little is known about its dynamics and role in transcriptional regulation of granulosa cells during chicken folliculogenesis. We investigate the transcriptomic dynamics of chicken granulosa cells over ten follicular stages and assess the chromatin architecture dynamics and how it influences gene expression in granulosa cells at three key stages: the prehierarchical small white follicles, the first largest preovulatory follicles, and the postovulatory follicles. Our results demonstrate the consistency between the global reprogramming of chromatin architecture and the transcriptomic divergence during folliculogenesis, providing ample evidence for compartmentalization rearrangement, variable organization of topologically associating domains, and rewiring of the long-range interaction between promoter and enhancers. These results provide key insights into avian reproductive biology and provide a foundational dataset for the future in-depth functional characterization of granulosa cells.

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Section: Resultsmentioning

confidence: 99%

Dynamic transcriptome and chromatin architecture in granulosa cells during chicken folliculogenesis

Ning

Zhang

et al. 2022

Nat Commun

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“…TNBC was suggested to be classified into four different subtypes [57]. KLF5 is highly expressed in basal-like breast cancers, including HCC1937 and HCC1806 cell lines, in contrast, KLF5 is lowly expressed in MDA-MB-231 cell line [20]. HDACi also decreased the KLF5 protein expression levels in two different BLBC cell lines, such as BT549 and SUM149PT (Fig.…”

Section: Discussionmentioning

confidence: 97%

“…Previous studies have shown that high expression levels of KLF5 are significantly associated with an increased risk of recurrence and poor prognosis in breast cancer patients [19]. KLF5 is a potential therapeutic target for BLBC [20]. KLF5 depletion suppresses BLBC initiation, growth, and metastasis [17,21].…”

Section: Ivyspringmentioning

confidence: 99%

Histone Deacetylase Inhibitors (HDACi) Promote KLF5 Ubiquitination and Degradation in Basal-like Breast Cancer

Kong¹,

Ren²,

Fang³

et al. 2022

Int. J. Biol. Sci.

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Basal-like breast cancer (BLBC) accounts for approximately 15% of all breast cancer cases, and patients with BLBC have a low survival rate. Our previous study demonstrated that the KLF5 transcription factor promotes BLBC cell proliferation and tumor growth. In this study, we demonstrated that the histone deacetylase inhibitors (HDACi), suberoylanilide hydroxamic acid (SAHA), and trichostatin A (TSA), increased KLF5 acetylation at lysine 369 (K369), downregulated KLF5 protein expression levels, and decreased cell viability in BLBC cell lines. HDACi target KLF5 for proteasomal degradation by promoting KLF5 protein ubiquitination. K369 acetylation of KLF5 decreases the binding between KLF5 and its deubiquitinase, BAP1. These findings revealed a novel mechanism by which HDACi suppress BLBC, and a novel crosstalk between KLF5 protein acetylation and ubiquitination.

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“…Textmining STRING [71] interacts with GATA4 and GATA6 [90] was the regulator in KATO III gastric cancer cells. It is possible that the difference may arise from the different histopathological phenotypes because KATO III is a human gastric signet ring cell adenoma cancer that can be induced to adipogenic, chondrogenic, osteogenic, and neurogenic differentiation [91].…”

Section: Mfhas1mentioning

confidence: 99%

Transcriptional and Epigenetic Bioinformatic Analysis of Claudin-9 Regulation in Gastric Cancer

Hernández-Nava

Montaño

Rendón-Huerta

2021

Journal of Oncology

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Gastric cancer is a heterogeneous disease that represents 5% to 10% of all new cancer cases worldwide. Advances in histological diagnosis and the discovery of new genes have admitted new genomic classifications. Nevertheless, the bioinformatic analysis of gastric cancer databases has favored the detection of specific differentially expressed genes with biological significance. Claudins, a family of proteins involved in tight junction physiology, have emerged as the key regulators of cellular processes, such as growth, proliferation, and migration, associated with cancer progression. The expression of Claudin-9 in the gastric cancer tissue has been linked to poor prognosis, however, its transcriptional and epigenetic regulations demand a more comprehensive analysis. Using the neural network promoter prediction, TransFact, Uniprot-KB, Expasy-SOPMA, protein data bank, proteomics DB, Interpro, BioGRID, String, and the FASTA protein sequence databases and software, we found the following: (1) the promoter sequence has an unconventional structure, including different transcriptional regulation elements distributed throughout it, (2) GATA 4, GATA 6, and KLF5 are the key regulators of Claudin-9 expression, (3) Oct1, NF-κB, AP-1, c-Ets-1, and HNF-3β have the higher binding affinity to the CLDN9 promoter, (4) Claudin-9 interacts with cell differentiation and development proteins, (5) CLDN9 is highly methylated, and (6) Claudin-9 expression is associated with poor survival. In conclusion, Claudin-9 is a protein that should be considered a diagnostic marker as its gene promoter region binds to the transcription factors associated with the deregulation of cell control, enhanced cell proliferation, and metastasis.

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The roles and regulation of the KLF5 transcription factor in cancers

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 74 publications

References 202 publications

Dynamic transcriptome and chromatin architecture in granulosa cells during chicken folliculogenesis

Dynamic transcriptome and chromatin architecture in granulosa cells during chicken folliculogenesis

Histone Deacetylase Inhibitors (HDACi) Promote KLF5 Ubiquitination and Degradation in Basal-like Breast Cancer

Transcriptional and Epigenetic Bioinformatic Analysis of Claudin-9 Regulation in Gastric Cancer

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