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In vitro methylation studies in multiple human cell types [HumanMethylation850 array]

ABSTRACT: In vitro methylation studies in multiple human cell types [HumanMethylation850 array]

PROVIDER: PRJNA811635 | ENA |

REPOSITORIES: ENA

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In vitro methylation studies in multiple human cell types [HumanMethylation450 array]

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In vitro methylation studies in multiple human cell types

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In vitro methylation studies in multiple human cell types [HumanMethylation450 array]

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In vitro methylation studies in multiple human cell types

Project description:This SuperSeries is composed of the SubSeries listed below.

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A specific JMJD6 inhibitor potently suppresses multiple types of cancers both in vitro and in vivo

Project description:Jumonji C-domain containing protein 6 (JMJD6), an iron (Fe2+) and a-ketoglutarate (a-KG)-dependent oxygenase, is expressed at high levels, correlated with poor prognosis, and considered as a therapeutic target in multiple cancer types. However, specific JMJD6 inhibitors that are potent in suppressing tumorigenesis have not been reported so far. We herein report that iJMJD6, a specific small-molecule inhibitor of JMJD6 with favorable physiochemical properties, inhibits the enzymatic activity of JMJD6 protein both in vitro and in cultured cells. iJMJD6 is effective in suppressing cell proliferation, migration, and invasion in multiple types of cancer cells in a JMJD6-dependent manner, while it exhibits minimal toxicity in normal cells. Mechanistically, iJMJD6 represses the expression of oncogenes including Myc and CCND1, in accordance with JMJD6 function in promoting the transcription of these genes. iJMJD6 exhibits suitable pharmacokinetic properties and suppresses tumor growth in multiple cancer cell line-and patient-derived xenograft models with safety. Furthermore, combination therapy with iJMJD6 and BET protein inhibitor (BETi) JQ1 or estrogen receptor antagonist fulvestrant exhibits synergistic effects in suppressing tumor growth. Taken together, we demonstrate that inhibition of JMJD6 enzymatic activity by using iJMJD6 is effective in suppressing oncogene expression and cancer development, providing a therapeutic avenue for treating cancers that are dependent on JMJD6 in clinic.

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