JARID2 coordinates with the NuRD complex to facilitate breast tumorigenesis through response to adipocyte‐derived leptin

作者：Wei Liu, Yi Zeng, Xinhui Hao, Xin Wang, Jiaxiang Liu, Tianyang Gao, Mengdi Wang, Jingyao Zhang, Miaomiao Huo, Ting Hu, Tianyu Ma, Die Zhang, Xu Teng, Hefen Yu, Min Zhang, Baowen Yuan, Wei Huang, Yunkai Yang, Yan Wang · 发表于：癌症：英文版 · 年份：2023 · DOI：10.1002/cac2.12479 · 被引用次数：23 · 研究领域：Regulation of Appetite and Obesity、Adipose Tissue and Metabolism、GDF15 and Related Biomarkers

BACKGROUND: Proteins containing the Jumonji C (JmjC) domain participated in tumorigenesis and cancer progression. However, the mechanisms underlying this effect are still poorly understood. Our objective was to investigate the role of Jumonji and the AT-rich interaction domain-containing 2 (JARID2) - a JmjC family protein - in breast cancer, as well as its latent association with obesity. METHODS: Immunohistochemistry, The Cancer Genome Atlas, Gene Expression Omnibus, and other databases were used to analyze the expression of JARID2 in breast cancer cells. Growth curve, 5-ethynyl-2-deoxyuridine (EdU), colony formation, and cell invasion experiments were used to detect whether JARID2 affected breast cancer cell proliferation and invasion. Spheroidization-based experiments and xenotumor transplantation in NOD/SCID mice were used to examine the association between JARID2 and breast cancer stemness. RNA-sequencing, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis were used to identify the cell processes in which JARID2 participates. Immunoaffinity purification and silver staining mass spectrometry were conducted to search for proteins that might interact with JARID2. The results were further verified using co-immunoprecipitation and glutathione S-transferase (GST) pull-down experiments. Using chromatin immunoprecipitation (ChIP) sequencing, we sought the target genes that JARID2 and metastasis-associated protein 1 (MTA1) jointly regulated; the results wer...