ZC3H12A inhibits tumor growth and metastasis of breast cancer under hypoxic condition via the inactivation of IL-17 signaling pathway.

Luo, Zhongbing; Yang, Fulan; Liu, Kang; Ding, Zhenluo

Luo, Zhongbing; Yang, Fulan; Liu, Kang; Ding, Zhenluo.

Afiliación

Luo Z; Department of Breast Surgery, Ganzhou People's Hospital, Ganzhou City, Jiangxi Province, China.
Yang F; Department of Breast Surgery, Ganzhou People's Hospital, Ganzhou City, Jiangxi Province, China.
Liu K; Department of Breast Surgery, Ganzhou People's Hospital, Ganzhou City, Jiangxi Province, China.
Ding Z; Department of Breast Surgery, Ganzhou People's Hospital, Ganzhou City, Jiangxi Province, China.

Cell Cycle ; 23(2): 188-204, 2024 Jan.

Article en En | MEDLINE | ID: mdl-38357935

ABSTRACT

ABSTRACT

Hypoxia is a major contributor to tumor microenvironment (TME) and metastasis in most solid tumors. We seek to screen hypoxia-related genes affecting metastasis in breast cancer and to reveal relative potential regulatory pathway. Based on gene expression profiling of GSE17188 dataset, differential expressed genes (DEGs) were identified between highly metastatic breast cancer cells under hypoxia and samples under normoxia. The protein-protein interaction (PPI) network was utilized to determine hub genes. The gene expression profiling interactive analysis database (GEPIA2) and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were employed to quantify hub genes. Moreover, overexpression of zinc finger CCCH-type containing 12A (ZC3H12A) was performed both in breast cancer cells and xenograft mouse model to determine the role of ZC3H12A. We identified 134 DEGs between hypoxic and normoxic samples. Based on PPI analysis, 5 hub genes interleukin (IL)-6, GALN (GAL), CD22 molecule (CD22), ZC3H12A and TNF receptor associated factor 1 (TRAF1) were determined; the expression levels of TRAF1, IL-6, ZC3H12A and GAL were remarkably downregulated while CD22 was upregulated in breast cancer cells. Besides, patients with higher expression of ZC3H12A had favorable prognosis. Overexpression of ZC3H12A could inhibit metastasis and tumor growth of breast cancer; overexpression of ZC3H12A downregulated the expression of IL-17 signaling pathway-related proteins such as IL-17 receptor A (IL-17RA), IL-17A and nuclear factor κB activator 1 (Act1). This study reveals ZC3H12A and IL-17 signaling pathway as potential therapeutic targets for hypoxic breast cancer.

Asunto(s)

Neoplasias de la Mama; Proliferación Celular; Regulación Neoplásica de la Expresión Génica; Interleucina-17; Ratones Desnudos; Transducción de Señal; Humanos; Neoplasias de la Mama/patología; Neoplasias de la Mama/genética; Neoplasias de la Mama/metabolismo; Femenino; Transducción de Señal/genética; Interleucina-17/metabolismo; Interleucina-17/genética; Animales; Línea Celular Tumoral; Ratones; Proliferación Celular/genética; Metástasis de la Neoplasia; Ratones Endogámicos BALB C; Mapas de Interacción de Proteínas/genética; Microambiente Tumoral/genética; Hipoxia de la Célula/genética; Perfilación de la Expresión Génica; Factores de Transcripción/metabolismo; Factores de Transcripción/genética

Palabras clave

Breast cancer; hypoxia; interleukin-17 signaling pathway; zinc finger CCCH-type containing 12A

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Transducción de Señal / Regulación Neoplásica de la Expresión Génica / Interleucina-17 / Proliferación Celular / Ratones Desnudos Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Cell Cycle Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos

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