TFCP2 Genetic Polymorphism Is Associated with Predisposition to and Transplant Prognosis of Hepatocellular Carcinoma

Liu, Zhikun; Gao, Feng; Shao, Zhimin; Xie, Haiyang; Zhou, Lin; Xu, Xiao

doi:10.1155/2017/6353248

Cited by 3 publications

(2 citation statements)

References 24 publications

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“…The transcription factor CP2 (TFCP2) was first identified as an onco-protein in liver cancer in 2010 (Yoo et al, 2010). Thereafter, most studies focusing on TFCP2 function were performed in liver cancer cells (Liu et al, 2017), presumably because of the essential pro-carcinogenic roles of TFCP2 in liver tumorigenesis. TFCP2 has been shown to stimulate the transcription of metastasis-promoting genes, such as matrix metalloproteinase-9 (MMP-9), fibronectin 1 (FN1), and tight junction protein 1 (TJP1) (Santhekadur et al, 2012;Xu et al, 2015), suggesting that TFCP2 acts as a transcription factor to bind gene promoters.…”

Section: Introductionmentioning

confidence: 99%

TFCP2 Is Required for YAP-Dependent Transcription to Stimulate Liver Malignancy

et al. 2017

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Although YAP-dependent transcription is closely associated with liver tumorigenesis, the mechanism by which YAP maintains its function is poorly understood. Here, we show that TFCP2 is required for YAP-dependent transcription and liver malignancy. Mechanistically, YAP function is stimulated by TFCP2 via a WW-PSY interaction. TFCP2 also maintains YAP stability by inhibiting βTrCP. Notably, genomic co-occupancy of YAP and TFCP2 is revealed. TFCP2 acts as a transcription co-factor that stimulates YAP transcription by facilitating YAP binding with YAP binding motif (YBF)-containing transcription factors. Interestingly, TFCP2 also stimulated the YAP-TEAD interaction and TEAD target gene expression. Finally, several genes co-regulated by YAP and TFCP2 that contribute to YAP-dependent tumorigenesis are identified and verified. Thus, we establish a model showing that TFCP2 acts as a YAP co-factor to maintain YAP-dependent transcription in liver cancer cells, suggesting that simultaneous targeting of both YAP and TFCP2 may be an effective therapeutic approach.

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Section: Introductionmentioning

confidence: 99%

TFCP2 Is Required for YAP-Dependent Transcription to Stimulate Liver Malignancy

et al. 2017

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“…The TF, TFCP2, plays a crucial role in cancer incidence and development [ 29 ]. The TFCP2 / TFCP2L1 / UBP1 TF subfamily is involved in various aspects of cancer development [ 30 ], including roles as pro-oncogenic factors in hepatocellular carcinoma as well as pancreatic and breast cancer.…”

Section: Discussionmentioning

confidence: 99%

DNA hypermethylation contributes to colorectal cancer metastasis by regulating the binding of CEBPB and TFCP2 to the CPEB1 promoter

Shao

Zhang

et al. 2021

Clin Epigenet

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Background Aberrant DNA methylation has been firmly established as a factor contributing to the pathogenesis of colorectal cancer (CRC) via its capacity to silence tumour suppressor genes. However, the methylation status of multiple tumour suppressor genes and their roles in promoting CRC metastasis are not well characterised. Methods We explored the methylation and expression profiles of CPEB1 (the gene encoding cytoplasmic polyadenylation element-binding protein 1), a candidate CRC tumour suppressor gene, using The Cancer Genome Atlas (TCGA) database and validated these results in both CRC cell lines and cells from Han Chinese CRC patients (n = 104). The functional role of CPEB1 in CRC was examined in experiments performed in vitro and in vivo. A candidate transcription factor capable of regulating CPEB1 expression was predicted in silico and validated by luciferase reporter, DNA pull-down, and electrophoretic mobility shift assays. Results Hypermethylation and decreased expression of CPEB1 in CRC tumour tissues were revealed by TCGA database. We also identified a significant inverse correlation (Pearson’s R = − 0.43, P < 0.001) between promoter methylation and CPEB1 expression. We validated these results in CRC samples and two CRC cell lines. We also demonstrated that up-regulation of CPEB1 resulted in significantly decreased tumour growth, migration, invasion, and tumorigenicity and promoted tumour cell apoptosis both in vitro and in vivo. We identified the transcription factors CCAAT enhancer-binding protein beta (CEBPB) and transcription factor CP2 (TFCP2) as critical regulators of CPEB1 expression. Hypermethylation of the CPEB1 promoter resulted in a simultaneous increase in the capacity for TFCP2 binding and a decreased likelihood of CEBPB binding, both of which led to diminished expression of CPEB1. Conclusions Our results identified a novel tumour-suppressive role of CPEB1 in CRC and found that hypermethylation of the CPEB1 promoter may lead to diminished expression due to decreased chromatin accessibility and transcription factor binding. Collectively, these results suggest a potential role for CPEB1 in the diagnosis and treatment of CRC.

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