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SOHLH2 Suppresses Angiogenesis by Downregulating HIF1α Expression in Breast Cancer.
Cui, Weiwei; Xiao, Yunling; Zhang, Ruihong; Zhao, Na; Zhang, Xianghong; Wang, Fuwu; Liu, Yang; Zhang, Xiaoli; Hao, Jing.
Afiliação
  • Cui W; Key Laboratory of The Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P.R. China.
  • Xiao Y; Department of Geriatric Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P.R. China.
  • Zhang R; Key Laboratory of The Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P.R. China.
  • Zhao N; Key Laboratory of The Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P.R. China.
  • Zhang X; Research platform in School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P.R. China.
  • Wang F; Key Laboratory of The Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P.R. China.
  • Liu Y; Key Laboratory of The Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P.R. China.
  • Zhang X; Key Laboratory of The Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P.R. China. haojing@sdu.edu.cn zhangxiaoli@sdu.edu.cn.
  • Hao J; Key Laboratory of The Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P.R. China. haojing@sdu.edu.cn zhangxiaoli@sdu.edu.cn.
Mol Cancer Res ; 19(9): 1498-1509, 2021 09.
Article em En | MEDLINE | ID: mdl-34158392
SOHLH2 has been demonstrated the downregulation in various cancers and the involvement in tumor growth and metastasis. However, the function of SOHLH2 on tumor angiogenesis and the underlying molecular mechanisms have not been interrogated. IHC staining results revealed that SOHLH2 was negatively associated with microvessel density (MVD), tumor size, histology grade, and metastasis. Overexpression of SOHLH2 inhibited the angiogenic behavior of human umbilical vein endothelial cells (HUVEC) by a tumor cell-mediated paracrine signal, while knockdown of SOHLH2 promoted HUVEC angiogenic behavior. Ectopic SOHLH2 expression remarkably suppressed tumor growth and MVD in xenograft tumors, downregulated the expression of hypoxia inducible factor-1 alpha (HIF1α)-mediated proangiogenic genes in vivo and in vitro, while knockdown of SOHLH2 had an opposite result. Furthermore, we found that upregulation of HIF1α reversed SOHLH2-induced suppression of breast cancer angiogenesis, while KC7F2, the inhibitor of HIF1α, could attenuate the promotion of angiogenesis by SOHLH2 silencing. Using Chromatin immunoprecipitation and luciferase reporter assays, we validated that SOHLH2 could directly bind to HIF1α promoter and repress its transcriptional activity. Collectively, SOHLH2 suppresses breast cancer angiogenesis by downregulating HIF1α transcription and may be a potential biomarker for anti-angiogenesis therapy. IMPLICATIONS: SOHLH2 directly represses HIF1α-mediated angiogenesis and serves as an important inhibitor of angiogenesis in breast cancer.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Biomarcadores Tumorais / Regulação Neoplásica da Expressão Gênica / Fatores de Transcrição Hélice-Alça-Hélice Básicos / Subunidade alfa do Fator 1 Induzível por Hipóxia / Células Endoteliais da Veia Umbilical Humana / Neovascularização Patológica Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Biomarcadores Tumorais / Regulação Neoplásica da Expressão Gênica / Fatores de Transcrição Hélice-Alça-Hélice Básicos / Subunidade alfa do Fator 1 Induzível por Hipóxia / Células Endoteliais da Veia Umbilical Humana / Neovascularização Patológica Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article