Prognostic and diagnostic relevance of hypermethylated in cancer 1 (HIC1) CpG island methylation in renal cell carcinoma

Eggers, H.; Steffens, Sandra; Großhennig, Anika; Becker, Jan U.; Hennenlotter, Joerg; Stenzl, Arnulf; Merseburger, Axel S.; Kuczyk, Markus A.; Serth, Jürgen

doi:10.3892/ijo.2012.1367

Cited by 15 publications

(15 citation statements)

References 32 publications

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“…Moreover, HIC-1 expression was found to be silenced in triple-negative breast cancer [24]. Although studies have identified HIC-1 as having frequent changes in hypermethylation or loss of heterozygosity in many human cancers [40, 41], the molecular mechanisms through which HIC-1 inhibits cancer progression remain poorly understood. HIC-1 is a multifunctional, sequence-specific transcriptional repressor that interacts with several major repression and chromatin remodeling complexes [42, 43].…”

Section: Discussionmentioning

confidence: 99%

Downregulation of hypermethylated in cancer-1 by miR-4532 promotes adriamycin resistance in breast cancer cells

et al. 2018

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BackgroundMicroRNAs are small RNAs (~ 22 nt) that modulate the expression of thousands of genes in tumors and play important roles in the formation of multidrug resistance. In this study, we firstly investigated that miR-4532 involved in the multidrug resistance formation of breast cancer by targeting hypermethylated in cancer 1 (HIC-1), a tumor-suppressor gene.MethodsTo identify and characterize the possible miRNAs in regulating multidrug resistance, we employed the transcriptome sequencing approach to profile the changes in the expression of miRNAs and their target mRNAs were obtained by bioinformatics prediction. Then the molecular biology experiments were conducted to confirm miR-4532 involved in multidrug resistance formation of breast cancer.ResultsThe luciferase reporter assay experiment was employed to confirm that HIC-1 was the target of miR-4532. Transfection with an miR-4532 mimic indicated miR-4532 mimic significantly increased breast cancer cell resistance to adriamycin. Cell proliferation and invasion assay experiments showed overexpression of HIC-1 inhibited the invasion and metastasis of breast cancer cells. Meanwhile, the interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) signaling pathway was confirmed to be involving in multidrug resistance by western blotting experiments.ConclusionsThese results suggest that downregulation of hypermethylated in cancer-1 by miR-4532 could promote adriamycin resistance in breast cancer cells, in which the IL-6/STAT3 pathway was regulated by the HIC-1. This finding might contribute to new therapeutic target for reversal of tumor resistance.Electronic supplementary materialThe online version of this article (10.1186/s12935-018-0616-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Downregulation of hypermethylated in cancer-1 by miR-4532 promotes adriamycin resistance in breast cancer cells

et al. 2018

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“…Hypermethylated in cancer-1 ( HIC1 ), a tumor suppressor gene essential to mammalian development [4], is located in the chromosomal regions 17p13.3, and is telomeric to the TP53. In many different human cancers (including prostate [5–7], hepatocellular [8, 9], pancreatic [10], renal cell carcinoma [11], breast cancers [12] and esophageal cancers [13], HIC1 is epigenetically inactivated but not mutated [14]. The methylation status of the HIC1 promoter is also associated with tumorigenesis and poor survival in patients with medulloblastomas [15].…”

Section: Introductionmentioning

confidence: 99%

Hypermethylation of the HIC1 promoter and aberrant expression of HIC1/SIRT1 contribute to the development of thyroid papillary carcinoma

Zhang

Lin

et al. 2016

Oncotarget

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Hypermethylation leading to the loss of hypermethylated in cancer-1 (HIC1) gene expression occurs in many different types of human cancer. HIC1 is a transcriptional repressor that directly binds to the promoter region of NAD-dependent deacetylase sirtuin-1 (SIRT1). SIRT1 functions in cell growth, is anti-apoptotic, protect neurons, functions in senescence, and regulates energy restriction. Epigenetic modification and dysregulation affecting the HIC1/SIRT1 axis is potentially important for the development of malignancies. However, the importance of HIC1 expression in the development of papillary thyroid carcinoma, especially in Chinese patients, is uncertain. Therefore, we assessed the level of methylation in the HIC1 promoter and the mRNA and protein expression levels of HIC1 and SIRT1 in human thyroid papillary carcinoma and tumor adjacent control tissues. The demethylation reagent 5-aza-2′-deoxyctidine (5-aza-dc) and an HIC1 overexpression plasmid were used to manipulate the HIC1/SIRT1 pathway, and the effects on cell senescence, apoptosis, and cell cycle progression were assessed. Compared to normal thyroid tissue, thyroid tumors had lower expression of HIC1 and higher SIRT1 expression. The level of HIC1 methylation was also higher in thyroid carcinoma tissues than adjacent tissues. HIC1 expression was closely correlated with patient age and tumor progression. Restoration of HIC1 expression through an overexpression plasmid or 5-aza-dC treatment reduced SIRT1 expression and cell proliferation, and led to senescence, cell cycle arrest, and apoptosis. Aberrant expression of HIC1/SIRT1 and hypermethylation of the HIC1 promoter may be critical for the development and progression of papillary thyroid cancer.

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“…For example, hypermethylation of RASSF1A and HIC in patients with RCC is associated with a poor prognosis [79, 80]. …”

Section: Methodsmentioning

confidence: 99%

Epigenetic therapy in urologic cancers: an update on clinical trials

et al. 2016

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Epigenetic dysregulation is one of many factors that contribute to cancer development and progression. Numerous epigenetic alterations have been identified in urologic cancers including histone modifications, DNA methylation changes, and microRNA expression. Since these changes are reversible, efforts are being made to develop epigenetic drugs that restore the normal epigenetic patterns of cells, and many clinical trials are already underway to test their clinical potential. In this review we analyze multiple clinical trials (n=51) that test the efficacy of these drugs in patients with urologic cancers. The most frequently used epigenetic drugs were histone deacetylase inhibitors followed by antisense oligonucleotides, DNA methyltransferase inhibitors and histone demethylase inhibitors, the last of which are only being tested in prostate cancer. In more than 50% of the clinical trials considered, epigenetic drugs were used as part of combination therapy, which achieved the best results. The epigenetic regulation of some cancers is still matter of research but will undoubtedly open a window to new therapeutic approaches in the era of personalized medicine. The future of therapy for urological malignancies is likely to include multidrug regimens in which epigenetic modifying drugs will play an important role.

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Prognostic and diagnostic relevance of hypermethylated in cancer 1 (HIC1) CpG island methylation in renal cell carcinoma

Cited by 15 publications

References 32 publications

Downregulation of hypermethylated in cancer-1 by miR-4532 promotes adriamycin resistance in breast cancer cells

Downregulation of hypermethylated in cancer-1 by miR-4532 promotes adriamycin resistance in breast cancer cells

Hypermethylation of the HIC1 promoter and aberrant expression of HIC1/SIRT1 contribute to the development of thyroid papillary carcinoma

Epigenetic therapy in urologic cancers: an update on clinical trials

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