Menin Coordinates C/EBPβ-Mediated TGF-β Signaling for Epithelial-Mesenchymal Transition and Growth Inhibition in Pancreatic Cancer

Peng, Cheng; Chen, Ying; He, Tianlin; Wang, Chao; Guo, Shiwei; Hu, Hao; Ni, Chenming; Jin, Gang; Zhang, Yijie

doi:10.1016/j.omtn.2019.08.013

Cited by 20 publications

(15 citation statements)

References 38 publications

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“…Previous studies have shown that C/EBP β was involved in cancer cell growth and tumor progression [ 28 – 30 ], including breast cancer, Pancreatic cancer etc. Our study has revealed that C/EBP β promotes proliferation, migration and invasion in ESCC cells (Sup Fig.…”

Section: Resultsmentioning

confidence: 99%

KDM6B promotes ESCC cell proliferation and metastasis by facilitating C/EBPβ transcription

Qin

Han

et al. 2021

BMC Cancer

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Background As an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression, KDM6B has been implicated in the development and malignant progression in various types of cancers. However, its potential roles in esophageal squamous cell carcinoma (ESCC) have not been explored. Methods The expression of KDM6B in human ESCC tissues and cell lines was examined using RT-qPCR, immunohistochemical staining and immunoblotting. The effects of KDM6B on the proliferation and metastasis of ESCC were examined using in vitro and in vivo functional tests. RNA-seq and ChIP-seq assay were used to demonstrate the molecular biological mechanism of KDM6B in ESCC. Results We show that the expression level of KDM6B increased significantly in patients with lymph node metastasis. Furthermore, we confirmed that KDM6B knockdown reduces proliferation and metastasis of ESCC cells, while KDM6B overexpression has the opposite effects. Mechanistically, KDM6B regulates TNFA_SIGNALING_VIA_NFκB signalling pathways, and H3K27me3 binds to the promoter region of C/EBPβ, leading to the promotion of C/EBPβ transcription. Besides, we show that GSK-J4, a chemical inhibitor of KDM6B, markedly inhibits proliferation and metastasis of ESCC cells. Conclusions The present study demonstrated that KDM6B promotes ESCC progression by increasing the transcriptional activity of C/EBPβ depending on its H3K27 demethylase activity.

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Section: Resultsmentioning

confidence: 99%

KDM6B promotes ESCC cell proliferation and metastasis by facilitating C/EBPβ transcription

Qin

Han

et al. 2021

BMC Cancer

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“…TGF-β-induced EMT has been implicated in tumor progression and metastasis in many types of carcinomas, including ccRCC. 23 , 24 , 25 , 26 However, our understanding of the mechanism underlying the regulation of TGF-β/Smad3 signaling during cancer metastasis remains limited. 27 , 28 In the present study, we provided evidence that demonstrated that lnc-TSI was an important regulator of the interaction between TβRI and Smad3 and negatively regulated TGF-β-induced EMT in ccRCC at the epigenetic and post-transcriptional levels.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: lncRNA lnc-TSI Inhibits Metastasis of Clear Cell Renal Cell Carcinoma by Suppressing TGF-β-Induced Epithelial-Mesenchymal Transition

Wang

Chen

et al. 2020

Molecular Therapy - Nucleic Acids

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The transforming growth factor-β (TGF-β)/Smads signal plays an important role in cancer metastasis by mediating the epithelial-mesenchymal transition (EMT) in cancer cells. lnc-TSI is a recently identified long noncoding RNA that negatively regulates the TGF-β/Smads signal. The present study was conducted to test the hypothesis that lnc-TSI inhibits metastasis in clear cell renal cell carcinoma (ccRCC) by regulating the TGF-β/Smad3 pathway. Herein, we show that lnc-TSI was upregulated in ccRCC cells and tissue and was associated with activation of the TGF-β/Smads signal. Depleting lnc-TSI enhanced tumor cell invasion and metastasis in vitro and ccRCC lung metastasis in vivo , whereas overexpressing lnc-TSI inhibited ccRCC cell invasion and tumor metastasis. Mechanistic studies indicated that lnc-TSI specifically inhibited the phosphorylation of Smad3 and subsequent EMT by binding with the MH2 domain of Smad3 to block the interaction between Smad3 and TGF-β receptor I in ccRCC cells. In a cohort of 150 patients with ccRCC, expression of lnc-TSI in tumors was negatively correlated with phosphorylated (p)Smad3 and activated EMT markers. Patients with expression of tumor lnc-TSI greater than or equal to the median at radical nephrectomy had a higher survival rate compared to those with lnc-TSI below the median during follow-up. These findings reveal a new regulatory mechanism of ccRCC metastasis and suggest a potential molecular target for the development of anti-cancer drugs.

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“…Previous studies have shown that C/EBPβ was involved in cancer cell growth and tumor progression [28][29][30], including breast cancer, Pancreatic cancer etc. Our study has revealed that C/EBPβ promotes proliferation, migration and invasion in ESCC cells (Supplementary Fig.…”

Section: Kdm6b-stimulated Proliferation and Metastasis Of Escc Cells mentioning

confidence: 99%

KDM6B Promotes ESCC Cell Proliferation and Metastasis by Facilitating C/EBPβ Transcription

qin

Han

et al. 2021

Preprint

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BackgroundAs an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression, KDM6B has been implicated in the development and malignant progression in various types of cancers. However, its potential roles in esophageal squamous cell carcinoma (ESCC) have not been explored. MethodsThe expression of KDM6B in human ESCC tissues and cell lines was examined using qRT-PCR, immunohistochemical staining and immunoblotting. The effects of KDM6B on the proliferation and metastasis of ESCC were examined using in vitro and in vivo functional tests. RNA-seq and ChIP-seq assay were used to demonstrate the molecular biological mechanism of KDM6B in ESCC.ResultsWe show that the expression level of KDM6B increased significantly in patients with lymph node metastasis. Furthermore, we confirmed that KDM6B knockdown reduces proliferation and metastasis of ESCC cells, while KDM6B overexpression has the opposite effects. Mechanistically, KDM6B regulates TNFA_SIGNALING_VIA_NFκB signalling pathways, and H3K27me3 binds to the promoter region of C/EBPβ, leading to the promotion of C/EBPβ transcription. Besides, we show that GSK-J4, a chemical inhibitor of KDM6B, markedly inhibits proliferation and metastasis of ESCC cells. ConclusionsThe present study demonstrated that KDM6B promotes ESCC progression by increasing the transcriptional activity of C/EBPβ depending on its H3K27 demethylase activity.

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Menin Coordinates C/EBPβ-Mediated TGF-β Signaling for Epithelial-Mesenchymal Transition and Growth Inhibition in Pancreatic Cancer

Cited by 20 publications

References 38 publications

KDM6B promotes ESCC cell proliferation and metastasis by facilitating C/EBPβ transcription

KDM6B promotes ESCC cell proliferation and metastasis by facilitating C/EBPβ transcription

RETRACTED: lncRNA lnc-TSI Inhibits Metastasis of Clear Cell Renal Cell Carcinoma by Suppressing TGF-β-Induced Epithelial-Mesenchymal Transition

KDM6B Promotes ESCC Cell Proliferation and Metastasis by Facilitating C/EBPβ Transcription

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