ArticleBMC cancer2011
SIP1 is downregulated in hepatocellular carcinoma by promoter hypermethylation.
Article in BMC cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 34 citations in OpenAlex.
- Hepatitis B virus X protein and TGF-β: partners in the carcinogenic journey of hepatocellular carcinoma.Frontiers in oncology · 2024Review
- Genome-wide cross-cancer analysis illustrates the critical role of bimodal miRNA in patient survival and drug responses to PI3K inhibitors.PLoS computational biology · 2022Article
- Methylation‑associated inactivation of JPH3 and its effect on prognosis and cell biological function in HCC.Molecular medicine reports · 2022Article
- Systematic Analysis of Cytostatic TGF-Beta Response in Mesenchymal-Like Hepatocellular Carcinoma Cell Lines.Journal of gastrointestinal cancer · 2021Article
- DNA methylation-driven EMT is a common mechanism of resistance to various therapeutic agents in cancer.Clinical epigenetics · 2020Article
- Genome-wide analysis of endogenously expressed ZEB2 binding sites reveals inverse correlations between ZEB2 and GalNAc-transferase GALNT3 in human tumors.Cellular oncology (Dordrecht, Netherlands) · 2018Article
- Article
- Roles and epigenetic regulation of epithelial-mesenchymal transition and its transcription factors in cancer initiation and progression.Cellular and molecular life sciences : CMLS · 2016Review
- SIP1 is a downstream effector of GADD45G in senescence induction and growth inhibition of liver tumor cells.Oncotarget · 2015Article
- Twist in hepatocellular carcinoma: pathophysiology and therapeutics.Hepatology international · 2015Review
- Genome-wide transcript profiling reveals novel breast cancer-associated intronic sense RNAs.PloS one · 2015Article
- Epithelial to mesenchymal transition inducing transcription factors and metastatic cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Review
- EMT-activating transcription factors in cancer: beyond EMT and tumor invasiveness.Cellular and molecular life sciences : CMLS · 2012Review
- Article
- Cell-free Circulating miRNA Biomarkers in Cancer.Journal of Cancer · 2012Article
- Expanding roles of ZEB factors in tumorigenesis and tumor progression.American journal of cancer research · 2011Article
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSmad interacting protein-1 is a transcription factor that is implicated in transforming growth factor-β/bone morphogenetic protein signaling and a repressor of E-cadherin and human telomerase reverse transcriptase. It is also involved in epithelial-mesenchymal transition and tumorigenesis. However, genetic and epigenetic alterations of SIP1 have not been fully elucidated in cancers. In this study, we investigated mutations and promoter hypermethylation of the SIP1 gene in human hepatocellular carcinomas.
methodsSIP1 expression was analyzed in HCC cell lines and primary tumors in comparison to normal and non-tumor liver tissues by using semi-quantitative RT-PCR, quantitative real-time RT-PCR and immunohistochemistry. Mutation and deletion screening of the SIP1 gene were performed by direct sequencing in HCC-derived cells. Restoration of SIP1 expression was sought by treating HCC cell lines with the DNA methyl transferase inhibitor, 5-AzaC, and the histone deacetylase inhibitor, TSA. SIP1 promoter methylation was analyzed by the combined bisulfite restriction analysis assay in in silico-predicted putative promoter and CpG island regions.
resultsWe found that the expression of SIP1 was completely lost or reduced in five of 14 (36%) HCC cell lines and 17 of 23 (74%) primary HCC tumors. Immunohistochemical analysis confirmed that SIP1 mRNA downregulation was associated with decreased expression of the SIP1 protein in HCC tissues (82.8%). No somatic mutation was observed in SIP1 exons in any of the 14 HCC cell lines. Combined treatment with DNA methyl transferase and histone deacetylase inhibitors synergistically restored SIP1 expression in SIP1-negative cell lines. Analysis of three putative gene regulatory regions revealed tumor-specific methylation in more than half of the HCC cases.
conclusionsEpigenetic mechanisms contribute significantly to the downregulation of SIP1 expression in HCC. This finding adds a new level of complexity to the role of SIP1 in hepatocarcinogenesis.
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