HMGN5 Escorts Oncogenic STAT3 Signaling by Regulating the Chromatin Landscape in Breast Cancer Tumorigenesis.

Autor:	Mou J; Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.; University of Chinese Academy of Sciences, Beijing, China., Huang M; ZJU-UoE Institute, Zhejiang University School of Medicine, International Campus, Zhejiang University, Haining, Zhejiang, China., Wang F; Nanjing University of Chinese Medicine, Nanjing, China., Xu X; Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China., Xie H; ZJU-UoE Institute, Zhejiang University School of Medicine, International Campus, Zhejiang University, Haining, Zhejiang, China., Lu H; Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China., Li M; ZJU-UoE Institute, Zhejiang University School of Medicine, International Campus, Zhejiang University, Haining, Zhejiang, China.; Department of Breast Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China., Li Y; Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China., Kong W; Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China., Chen J; Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.; University of Chinese Academy of Sciences, Beijing, China., Xiao Y; Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China., Chen Y; Department of Breast Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China., Wang C; ZJU-UoE Institute, Zhejiang University School of Medicine, International Campus, Zhejiang University, Haining, Zhejiang, China.; Department of Breast Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China., Ren J; Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.; University of Chinese Academy of Sciences, Beijing, China.
Jazyk:	angličtina
Zdroj:	Molecular cancer research : MCR [Mol Cancer Res] 2022 Dec 02; Vol. 20 (12), pp. 1724-1738.
DOI:	10.1158/1541-7786.MCR-22-0241
Abstrakt:	Cancer progression is highly dependent on the ability of cancer cell tumor formation, in which epigenetic modulation plays an essential role. However, the epigenetic factors promoting breast tumor formation are less known. Screened from three-dimensional (3D)-sphere tumor formation model, HMGN5 that regulates chromatin structures became the candidate therapeutic target in breast cancer, though its role is obscure. HMGN5 is highly expressed in 3D-spheres of breast cancer cells and clinical tumors, also an unfavorable prognostic marker in patients. Furthermore, HMGN5 controls tumor formation and metastasis of breast cancer cells in vitro and in vivo. Mechanistically, HMGN5 is governed by active STAT3 transcriptionally and further escorts STAT3 to shape the oncogenic chromatin landscape and transcriptional program. More importantly, interference of HMGN5 by nanovehicle-packaged siRNA effectively inhibits tumor growth in breast cancer cell-derived xenograft mice model. Implications: Our findings reveal a novel feed-forward circuit between HMGN5 and STAT3 in promoting breast cancer tumorigenesis and suggest HMGN5 as a novel epigenetic therapeutic target in STAT3-hyperactive breast cancer. (©2022 American Association for Cancer Research.)
Databáze:	MEDLINE
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