CPEB1 or CPEB4 knockdown suppresses the TAK1 and Smad signalings in THP-1 macrophage-like cells and dermal fibroblasts

Cui, Hui Song; Joo, So Young; Cho, Yoon Soo; Kim, June-Bum; Seo, Cheong Hoon

doi:10.1016/j.abb.2020.108322

Cited by 21 publications

(18 citation statements)

References 37 publications

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“…CPEB1 and CPEB4 has been shown to be positively associated with both canonical and non-canonical TGFβ signaling as their knockdown can attenuated TGFβ-activated expression levels of phosphorylated Smad 2, Smad 1/5/8, TAK1, P38, ERK, and JNK in fibroblasts. 47 The protein encoded by PRDM6 (putative histone-lysine N-methyltransferase), a member of the PRDM family, can act as a transcriptional repressor. The PRDM family members are recognized by their PR and multiple zinc-finger domains.…”

Section: Discussionmentioning

confidence: 99%

Global Gene Expression Regulation Mediated by TGFβ Through H3K9me3 Mark

2022

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Background: Epigenetic alterations play an important part in carcinogenesis. Different biological responses, including cell proliferation, migration, apoptosis, invasion, and senescence, are affected by epigenetic alterations in cancer. In addition, growth factors, such as transforming growth factor beta (TGFβ) are important regulators of tumorigenesis. Our understanding of the interplay between the epigenetic bases of tumorigenesis and growth factor signaling in tumorigenesis is rudimentary. Some studies suggest a link between TGFβ signaling and the heterochromatinizing histone mark H3K9me3. There is evidence for signal-dependent interactions between R-Smads and histone methyltransferases. However, the effects of TGFβ signaling on genome wide H3K9me3 landscape remains unknown. Our research examines TGFβ -induced genome-wide H3K9me3 in prostate cancer. Method: Chromatin-Immunoprecipitation followed by sequencing was performed to analyze genome-wide association of H3K9me3 epigenetic mark. DAVID Functional annotation tool was utilized to understand the involvement of different Biological Processes and Molecular Function. MEME-ChIP tool was also used to analyze known and novel DNA-binding motifs. Results: H3K9me3 occupancy appears to increase at intronic regions after short-term (6 hours) TGFβ stimulation and at distal intergenic regions during long-term stimulation (24 hours). We also found evidence for a possible association of SLC transporters with H3K9me3 mark in presence of TGFβ during tumorigenesis. No direct correlation was found between the occupancy of H3K9me3 mark and the expression of various genes. The epigenetic mechanisms-mediated regulation of gene expression by TGFβ was concentrated at promoters rich in SRY and FOXJ3 binding sites. Conclusion: Our results point toward a positive association of oncogenic function of TGFβ and the H3K9me3 mark and provide a context to the role of H3K9me3 in TGFβ-induced cell migration and cell adhesion. Interestingly, these functions of TGFβ through H3K9me3 mark regulation seem to depend on transcriptional activation in contrast to the conventionally known repressive nature of H3K9me3.

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Section: Discussionmentioning

confidence: 99%

Global Gene Expression Regulation Mediated by TGFβ Through H3K9me3 Mark

2022

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“…Upregulation of TAK1 promotes hepatocellular carcinoma tumorigenesis and metastasis [41]. And in the case of HS, previous study exhibited that reducing the levels of TAK1 can decrease TGF-β1induced fibrosis of dermal fibroblasts [42]. However, there is little research on the downstream regulation mechanism of TAK1 in HS.…”

Section: Discussionmentioning

confidence: 99%

LncRNA TUG1 exhibits pro-fibrosis activity in hypertrophic scar through TAK1/YAP/TAZ pathway via miR-27b-3p

Chen

et al. 2021

Mol Cell Biochem

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Hypertrophic Scar (HS) is a complicated fibrotic disease. In addition, its pathogenesis is still to be further explored. Long non-coding RNAs (lncRNAs) have been proved to be participated in multiple diseases, including HS. However, the role of lncRNA TUG1 in HS remains unclear. The expression level of RNA and protein in cells were detected by q-PCR and western blot, respectively. MTT assay was performed to test the cell proliferation. Cell migration was detected by transwell assay. Cell apoptosis was measured by flow cytometry. Dual luciferase report assay and RNA pull down were used to verify the relationship between TUG1, miR-27b-3p and TAK1.TUG1 and TAK1 were upregulated in HS, while miR-27b-3p was downregulated. Knockdown of TUG1 significantly suppressed the proliferation and migration and induced the apoptosis of HS fibroblasts (HSF). In addition, silencing of TUG1 notably inhibited the extracellular matrix (ECM) biosynthesis in HSF. Overexpression of miR-27b-3p has the same effect on HS as that of TUG1 knockdown. Meanwhile, TUG1 could sponge miR-27b-3p, and TAK1 was the direct target of miR-27b-3p. Furthermore, knockdown of TUG1 significantly suppressed the fibrosis in HS via miR-27b-3p/TAK1/YAP/TAZ axis mediation. LncRNA TUG1 promotes the fibrosis in HS via sponging miR-27b-3p and then activates TAK1/YAP/TAZ pathway, which may serve as a potential target for treatment of HS.

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“…CPEB1 and CPEB4 knockdowns also attenuated TGFβ-activated Smad-dependent and -independent signaling cascades by reducing the levels of TAK1, P38, ERK, JNK, and phosphorylated Smad 2 and Smad 1/5/8 in fibroblasts. 55 The protein encoded by PRDM6 (putative histone-lysine N-methyltransferase) is a transcriptional repressor and a member of the PRDM family. The PRDM family members contain a PR domain and multiple zinc-finger domains.…”

Section: Discussionmentioning

confidence: 99%

Global Histone H3 Lysine 4 Trimethylation (H3K4me3) Landscape Changes in Response to TGFβ

2021

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TGFβ expression acts as a biomarker of poor prognosis in prostate cancer. It plays a dual functional role in prostate cancer. In the early stages of the tumor, it acts as a tumor suppressor while at the later stages of tumor development, it promotes metastasis. The molecular mechanisms of action of TGFβ are largely understood through the canonical and non-canonical signal transduction pathways. Our understanding of the mechanisms that establish transient TGFβ stimulation into stable gene expression patterns remains incomplete. Epigenetic marks like histone H3 modifications are directly linked with gene expression and they play an important role in tumorigenesis. In this report, we performed chromatin immunoprecipitation-sequencing (ChIP-Seq) to identify the genome-wide regions that undergo changes in histone H3 Lysine 4 trimethylation (H3K4me3) occupancy in response to TGFβ stimulation. We also show that TGFβ stimulation can induce acute epigenetic changes through the modulation of H3K4me3 signals at genes belonging to special functional categories in prostate cancer. TGFβ induces the H3K4me3 on its own ligands like TGFβ, GDF1, INHBB, GDF3, GDF6, BMP5 suggesting a positive feedback loop. The majority of genes were found to be involved in the positive regulation of transcription from the RNA polymerase II promoter in response to TGFβ. Other functional categories were intracellular protein transport, brain development, EMT, angiogenesis, antigen processing, antigen presentation via MHC class II, lipid transport, embryo development, histone H4 acetylation, positive regulation of cell cycle arrest, and genes involved in mitotic G2 DNA damage checkpoints. Our results link TGFβ stimulation to acute changes in gene expression through an epigenetic mechanism. These findings have broader implications on epigenetic bases of acute gene expression changes caused by growth factor stimulation.

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CPEB1 or CPEB4 knockdown suppresses the TAK1 and Smad signalings in THP-1 macrophage-like cells and dermal fibroblasts

Cited by 21 publications

References 37 publications

Global Gene Expression Regulation Mediated by TGFβ Through H3K9me3 Mark

Global Gene Expression Regulation Mediated by TGFβ Through H3K9me3 Mark

LncRNA TUG1 exhibits pro-fibrosis activity in hypertrophic scar through TAK1/YAP/TAZ pathway via miR-27b-3p

Global Histone H3 Lysine 4 Trimethylation (H3K4me3) Landscape Changes in Response to TGFβ

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