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Inhibitor of binding/differentiation 2 (Id2) is regulated by CCAAT/enhancer-binding protein-? (C/EBP?) and promotes the proliferation of hepatocellular carcinoma.

ABSTRACT: Inhibitor of DNA binding/differentiation (Id2) is an important regulator involved in the initiation and progression of cancer. However, the function and mechanism of the regulation of Id2 in hepatocellular carcinoma (HCC) was unclear. In the present study, we found that the overexpression of Id2 increased HCC cell proliferation in vitro and in vivo. Knockdown of Id2 inhibited HCC cell proliferation in vitro and in vivo. Furthermore, knockdown of Id2 enhanced sorafenib-induced apoptosis in HCC. Conversely, overexpression of Id2 weakened sorafenib-induced apoptosis in HCC. In addition, the transcription factor CCAAT/enhancer-binding protein alpha (C/EBP?) bound to the Id2 promoter and decreased its expression in HCC cells. Therefore, all results suggest that Id2 promotes the proliferation of HCC cells by inhibiting cell apoptosis. Id2 may serve as a potential target in HCC therapy.

SUBMITTER: Liu Z

PROVIDER: S-EPMC6291656 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Inhibitor of binding/differentiation 2 (Id2) is regulated by CCAAT/enhancer-binding protein-α (C/EBPα) and promotes the proliferation of hepatocellular carcinoma.

Liu Zheng Z Yang Jing J Ge Chao C Zhao Fangyu F Li Hong H Yao Ming M Li Jinjun J Tian Hua H

American journal of cancer research 20181101 11

Inhibitor of DNA binding/differentiation (Id2) is an important regulator involved in the initiation and progression of cancer. However, the function and mechanism of the regulation of Id2 in hepatocellular carcinoma (HCC) was unclear. In the present study, we found that the overexpression of Id2 increased HCC cell proliferation in vitro and in vivo. Knockdown of Id2 inhibited HCC cell proliferation in vitro and in vivo. Furthermore, knockdown of Id2 enhanced sorafenib ...[more]

PMID: 30555742

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Project description:α-Synuclein is the main component of Lewy bodies, the intracellular protein aggregates representing the histological hallmark of Parkinson's disease. Elevated α-synuclein levels and mutations in SNCA gene are associated with increased risk for Parkinson's disease. Despite this, little is known about the molecular mechanisms regulating SNCA transcription. CCAAT/enhancer binding protein (C/EBP) β and δ are b-zip transcription factors that play distinct roles in neurons and glial cells. C/EBPβ overexpression increases SNCA expression in neuroblastoma cells and putative C/EBPβ and δ binding sites are present in the SNCA genomic region suggesting that these proteins could regulate SNCA transcription. Based on these premises, the goal of this study was to determine if C/EBPβ and δ regulate the expression of SNCA. We first observed that α-synuclein CNS expression was not affected by C/EBPβ deficiency but it was markedly increased in C/EBPδ-deficient mice. This prompted us to characterize further the role of C/EBPδ in SNCA transcription. C/EBPδ absence led to the in vivo increase of α-synuclein in all brain regions analyzed, both at mRNA and protein level, and in primary neuronal cultures. In agreement with this, CEBPD overexpression in neuroblastoma cells and in primary neuronal cultures markedly reduced SNCA expression. ChIP experiments demonstrated C/EBPδ binding to the SNCA genomic region of mice and humans and luciferase experiments showed decreased expression of a reporter gene attributable to C/EBPδ binding to the SNCA promoter. Finally, decreased CEBPD expression was observed in the substantia nigra and in iPSC-derived dopaminergic neurons from Parkinson patients resulting in a significant negative correlation between SNCA and CEBPD levels. This study points to C/EBPδ as an important repressor of SNCA transcription and suggests that reduced C/EBPδ neuronal levels could be a pathogenic factor in Parkinson's disease and other synucleinopathies and C/EBPδ activity a potential pharmacological target for these neurological disorders.

Dataset Information

Inhibitor of binding/differentiation 2 (Id2) is regulated by CCAAT/enhancer-binding protein-? (C/EBP?) and promotes the proliferation of hepatocellular carcinoma.

Publications

Inhibitor of binding/differentiation 2 (Id2) is regulated by CCAAT/enhancer-binding protein-α (C/EBPα) and promotes the proliferation of hepatocellular carcinoma.

Similar Datasets

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