Moonmoon Deb1, Dipta Sengupta1, Swayamsiddha Kar1, Sandip Kumar Rath1, Subhendu Roy2, Goutam Das3, Samir Kumar Patra4. 1. Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, National Institute of Technology, Rourkela, Odisha 769008, India; Department of Life Science, National Institute of Technology, Rourkela, Odisha 769008, India. 2. Drs. Tribedi & Roy Diagnostic Laboratory, 93, Park Street, Kolkata 700 016, India. 3. Department of Surgery, Calcutta National Medical College, Kolkata 7000 014, India. 4. Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, National Institute of Technology, Rourkela, Odisha 769008, India; Department of Life Science, National Institute of Technology, Rourkela, Odisha 769008, India. Electronic address: samirp@nitrkl.ac.in.
Abstract
BACKGROUND: Caveolin-1 (CAV1) is an important structural component of cellular caveolae involved in cell signaling. CAV1 gene on/off regulatory mechanism in multiple diseases, including cancer is not clearly understood. The tumor suppressor versus oncogene paradox of CAV1 during tumor development tempted us to investigate the role for the epigenetic drift of CAV1 gene regulation. METHODS: We have analyzed CAV1 gene expression and associated epigenetic marks (DNA methylation and histone 3 modifications) in the CAV1 promoter in two colon cancer cell lines, under treatment with well established epigenetic modulators, AZA, SAM, TSA and SFN at varying concentrations. CAV1 gene promoter DNA methylation and histone modifications were analyzed by DNA methylation specific PCR, bisulphite modification of DNA and ChIP analyses following PCR respectively. RESULTS: Ectopic expression of CAV1 by epigenetic modulators inhibits colon cancer cell growth. CAV1 promoter DNA remains unmethylated before and after treatment with epigenetic modulators, which confirmed that DNA methylation is not the regulator of CAV1 expression in colon cancer. There was enrichment of H3K4me3 and H3K9AcS10P and depletion of H3K9me3 modifications around the CAV1 promoter. CONCLUSIONS: Our data provides novel insight into the regulation of CAV1 gene by histone H3 modifications and enhance the amplitude of the cancer epigenome.
BACKGROUND:Caveolin-1 (CAV1) is an important structural component of cellular caveolae involved in cell signaling. CAV1 gene on/off regulatory mechanism in multiple diseases, including cancer is not clearly understood. The tumor suppressor versus oncogene paradox of CAV1 during tumor development tempted us to investigate the role for the epigenetic drift of CAV1 gene regulation. METHODS: We have analyzed CAV1 gene expression and associated epigenetic marks (DNA methylation and histone 3 modifications) in the CAV1 promoter in two colon cancer cell lines, under treatment with well established epigenetic modulators, AZA, SAM, TSA and SFN at varying concentrations. CAV1 gene promoter DNA methylation and histone modifications were analyzed by DNA methylation specific PCR, bisulphite modification of DNA and ChIP analyses following PCR respectively. RESULTS: Ectopic expression of CAV1 by epigenetic modulators inhibits colon cancer cell growth. CAV1 promoter DNA remains unmethylated before and after treatment with epigenetic modulators, which confirmed that DNA methylation is not the regulator of CAV1 expression in colon cancer. There was enrichment of H3K4me3 and H3K9AcS10P and depletion of H3K9me3 modifications around the CAV1 promoter. CONCLUSIONS: Our data provides novel insight into the regulation of CAV1 gene by histone H3 modifications and enhance the amplitude of the cancer epigenome.
Authors: Jia Long; Chan-Juan Zhang; Neng Zhu; Ke Du; Yu-Fang Yin; Xi Tan; Duan-Fang Liao; Li Qin Journal: Am J Cancer Res Date: 2018-05-01 Impact factor: 6.166