Histone deacetylase inhibitor SAHA epigenetically regulates miR-17-92 cluster and MCM7 to upregulate MICA expression in hepatoma

Yang, Huan; Lan, Peixiang; Hou, Zhaohua; Guan, Yun; Zhang, J; Xu, Wenfang; Tian, Zhigang; Zhang, C

doi:10.1038/bjc.2014.547

Cited by 101 publications

(88 citation statements)

References 50 publications

(63 reference statements)

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“…Here, for the first time, we demonstrated that several tumor suppressor miRs were reactivated upon SAHA treatment in HNSCC. Consistent with our work, other groups have reported SAHA-mediated alteration of miR expression profiles in lung, breast, liver, and pancreatic cancer [8,22,30,47]. Our results revealed that SAHA treatment profoundly increased the expression of miR-107.…”

Section: Discussionsupporting

confidence: 93%

Suberoylanilide hydroxamic acid inhibits growth of head and neck cancer cell lines by reactivation of tumor suppressor microRNAs

et al. 2016

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Summary Background microRNAs negatively regulate gene expression at the post-transcriptional level. Mounting evidence shows that miR expression is deregulated in human cancers including head and neck squamous cell carcinoma (HNSCC). Epigenetically silenced tumor suppressor miRs may be re-expressed upon treatment with histone deacetylases inhibitors. Suberoylanilide Hydroxamic Acid (SAHA) is a histone deacetylase inhibitor that is currently being investigated in clinical trials for HNSCC. We hypothesized that SAHA will re-express a set of tumor suppressor miRs and enhance the efficacy of cisplatin and radiation in HNSCC. Results In this study, miR expression profile was utilized to identify the tumor suppressor miRs that are re-expressed following SAHA treatment in HNSCC. Our data demonstrated that two tumor suppressor miRs, miR-107 and miR-138, were significantly up-regulated in CAL27 and SCC25 cell lines, following SAHA treatment. In addition to this, treatment with SAHA in a dose dependent manner significantly inhibited the cell proliferation, cell migration, and anchorage dependent clonogenic survival in CAL27 and SCC25 cell lines, respectively. Further, the expression of several oncogenes, PKCε, HIF1β, CDK6, and RhoC were down regulated in response to SAHA treatment. Additionally, we demonstrated that the combination treatment with SAHA and a chemotherapeutic drug cisplatin caused a significant reduction of cell growth compared to the single agent treatment. Conclusion Our data indicate that SAHA treatment results in reactivation of the silenced tumor suppressor miRs. Furthermore, this study emphasizes the usefulness of this drug as a novel combination therapy for HNSCC patients.

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Section: Discussionsupporting

confidence: 93%

Suberoylanilide hydroxamic acid inhibits growth of head and neck cancer cell lines by reactivation of tumor suppressor microRNAs

et al. 2016

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“…1; refs. [19][20][21][22]. Although the immunomodulatory activities of DNMTi and of HDACi are frequently overlapping, some preferential tropism of the 2 drug classes can be observed, essentially depending on the prevalent molecular mechanism regulating the specific target molecules.…”

Section: (2)mentioning

confidence: 99%

Molecular Pathways: At the Crossroads of Cancer Epigenetics and Immunotherapy

Maio

Covre

Fratta

et al. 2015

Clinical Cancer Research

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“…Considering the immunotherapy, suberoylanilide hydroxamic acid (SAHA, a HDAC inhibitor) regulates the expression of microRNA-17-92 cluster then epigenetically elevates the level of major histocompatibility complex class I-related chain molecules A (MICA) and maintains complex component 7 (MCM7) in hepatoma. The outcome is to enhance the sensitivity of HCC to natural killer cell-mediated lysis (33). Combined pharmaceutical treatment has also become a popular issue in cancer therapy.…”

Section: Applications Of Hdac Inhibitor For the Therapy Of Hccmentioning

confidence: 99%

Cytokeratin 18-associated Histone 3 Modulation in Hepatocellular Carcinoma: A Mini Review

Lai

Cheng

Lai

et al. 2017

CGP

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Abstract.Hepatocellular carcinoma (HCC) is a cancer with high incidence and mortality in Taiwan. HCC cells exhibit different morphological features in divergent shapes and having pleomorphic nuclei from normal liver cells. Microtubules (MTs), intermediate filaments (IFs), and microfilaments (MFs) are major components of the cytoskeleton that are essential to maintain the integrity of eukaryotic cells (1). Proper cross-linking structures among these cytoskeletal proteins are crucial for intracellular architectures and normal cellular morphology. Plectin exhibits the binding sites accessible to IFs, MTs and MFs rendering the interaction with a variety of cytoskeletal components to maintain the integrity of the cytoskeletal network (2). The rope-like IFs have a mean diameter of 10 nm and mainly play a role in maintaining the shape and mechanical integrity of a cell (3). In human hepatocytes, a cytokeratin (CK) pair composed of CK8 (type II, 52 kD) and CK18 (type I, 45 kD) renders IFs (4). CKs are required for maintaining the integrity of hepatocytes (5). Altered expression of keratin genes were associated with chronic hepatitis, increased hepatocyte fragility and decreased bile secretion (6).In eukaryotic nucleus, the organization and packaging of DNA are achieved by addition of histone proteins to form chromatin. Post-translational modifications of histones, such as acetylation, phosphorylation, methylation and ADPribosylation, frequently alter the structure of chromatin (7). Epigenetic modifications of histone, especially acetylation status, altering the chromatin structure are involved in gene expression and further intervened in the pathogenesis of cancer. Two types of enzymes, including histone acetyltransferases (HATs) and histone deacetylases (HDACs), affect the acetylation status of histones. Recently it was reported that alterations in the activities of HDACs, as well as aberrant acetylation of histone, lead to diseases including cancer (8). HDACs catalyze histone deacetylation and repress transcription of specific genes, such as p21, resulting in cell-cycle activation and cell proliferation (9).The investigation of histones in our laboratory originated in a study of CK18, in which we found that CK18 was coimmunoprecipitated with histone H3 in human HCC, but not in normal liver. We speculated that both histone H3 and CK18 were modulated in HCC, which was shown in the co-219

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Histone deacetylase inhibitor SAHA epigenetically regulates miR-17-92 cluster and MCM7 to upregulate MICA expression in hepatoma

Cited by 101 publications

References 50 publications

Suberoylanilide hydroxamic acid inhibits growth of head and neck cancer cell lines by reactivation of tumor suppressor microRNAs

Suberoylanilide hydroxamic acid inhibits growth of head and neck cancer cell lines by reactivation of tumor suppressor microRNAs

Molecular Pathways: At the Crossroads of Cancer Epigenetics and Immunotherapy

Cytokeratin 18-associated Histone 3 Modulation in Hepatocellular Carcinoma: A Mini Review

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