Epigenetic targeting of SLC30A3 by HDAC1 is related to the malignant phenotype of glioblastoma.

Longzhou Zhang, Zengjin Liu, Yang Dong, Lingchang Kong

IUBMB life 2021 May

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The epigenetic abnormality is believed as a major driver for cancer initiation. Histone modification plays a vital role in tumor formation and progression. Particularly, alteration in histone acetylation has been highly associated with gene expression, cell cycle, as well as carcinogenesis. By analyzing glioblastoma (GBM)-related microarray from the GEO database and conducting chromatin immunoprecipitation-sequencing (ChIP-seq), we discovered that solute carrier family 30 member 3 (SLC30A3), a super enhancer (SE)-regulated factor, was significantly reduced in GBM tissues. Furthermore, histone deacetylase 1 (HDAC1), overexpressed in GBM tissues, could inhibit SLC30A3 expression by promoting histone H3K27ac deacetylation modification of the SE region of SLC30A3. Our functional validation revealed that SLC30A3 can inhibit the growth and metastatic spread of GBM cells in vitro and in vivo, and can activate the MAPK signaling pathway to promote apoptosis of GBM cells. Moreover, overexpression of HDAC1 resulted in a significant increase in DNA replication activity, a significant decline in apoptosis and cell cycle arrest in GBM cells. In a word, these findings indicate that combined epigenetic targeting of SLC30A3 by HDAC1 and SE is potentially therapeutically feasible in GBM. © 2021 International Union of Biochemistry and Molecular Biology.

Citation

Longzhou Zhang, Zengjin Liu, Yang Dong, Lingchang Kong. Epigenetic targeting of SLC30A3 by HDAC1 is related to the malignant phenotype of glioblastoma. IUBMB life. 2021 May;73(5):784-799