Identification of the upstream regulators of KDM5B in gastric cancer
Autor: | Long-Fei Zhao, Feng-Yu Qi, Jin-Ge Zhang, Jing-Ru Pang, Hong-Mei Ren, Dan-Dan Shen, Li-Juan Zhao, Lin Qi, Hong-Min Liu, Yi-Chao Zheng |
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Rok vydání: | 2022 |
Předmět: |
Jumonji Domain-Containing Histone Demethylases
DNA Copy Number Variations Lysine Nuclear Proteins General Medicine DNA General Biochemistry Genetics and Molecular Biology Gene Expression Regulation Neoplastic Repressor Proteins MicroRNAs Stomach Neoplasms Cell Line Tumor Humans General Pharmacology Toxicology and Pharmaceutics Cell Proliferation |
Zdroj: | Life sciences. 298 |
ISSN: | 1879-0631 |
Popis: | Lysine-specific demethylase 5B (KDM5B) is an epigenetic regulator of chromatin that catalyzes the demethylation of histone 3 lysine 4. It is overexpressed in multiple cancer types and acts as a therapeutic target in cancer therapy. Nevertheless, its upstream regulatory pathway is not completely understood, prompting the search for the underlying biological factors driving KDM5B overexpression.A comprehensive analysis was performed to examine the association between KDM5B overexpression and copy number variation (CNV), somatic mutation, mRNA expression, miRNA expression, and clinical characters from The Cancer Genome Atlas database. Coexpression and function enrichment analyses were performed with KDM5B-coexpressed genes. The gastric cancer (GC) cell line MKN45 was utilized to verify the regulation of KDM5B using the transcription factor (TF) Yin Yang 1 (YY1) and miR-29a-3p.KDM5B was overexpressed and associated with poor prognosis in GC. KDM5B upregulation was driven by CNV amplification and DNA hypomethylation rather than by KDM5B mutations. Enrichment analysis revealed that KDM5B-coexpressed genes were primarily related to the transmembrane transport function and the ubiquitin-mediated proteolysis signaling pathway. As a TF, YY1 might bind to the KDM5B promoter region to regulate KDM5B expression. In addition, miR-29a-3p might bind to and negatively regulate KDM5B expression.Our results demonstrate that KDM5B expression is regulated via CNV amplification, DNA hypomethylation, and YY1 and miR-29a-3p; KDM5B expression regulation is associated with patient survival and tumor cell proliferation. |
Databáze: | OpenAIRE |
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