Activation of the G Protein-Coupled Bile Acid Receptor TGR5 Modulates the HCP5/miR-139-5p/DDIT4 Axis to Antagonize Cervical Cancer Progression.

Su, Jia; Zhao, Yiqi; Chen, Wei-Dong; Wang, Yan-Dong

Su, Jia; Zhao, Yiqi; Chen, Wei-Dong; Wang, Yan-Dong.

Afiliación

Su J; State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.
Zhao Y; State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.
Chen WD; Key Laboratory of Receptors-Mediated Gene Regulation and Drug Discovery, School of Basic Medical Science, Inner Mongolia Medical University, Hohhot 010107, China.
Wang YD; Key Laboratory of Receptors-Mediated Gene Regulation, School of Basic Medical Sciences, Henan University, Kaifeng 475001, China.

Int J Mol Sci ; 25(16)2024 Aug 16.

Article en En | MEDLINE | ID: mdl-39201624

ABSTRACT

ABSTRACT

A growing body of evidence indicates that the G protein-coupled bile acid receptor, TGR5, plays a critical role in multiple physiological processes ranging from metabolic disorders to cancers. However, the biological functions of TGR5 in cervical cancer (CC) have not been elucidated. Here, using TGR5 knockout mice, we found that a deficiency of TGR5 leads to greater sensitivity to the progression of cervical inflammation. Activation of TGR5 by its specific ligands significantly attenuated the malignant behavior of CC cells. In addition, we found that TGR5 can negatively modulate the expression of lncRNA HCP5 by blocking its transcription activation when mediated by p65. HCP5 was highly expressed in CC tissues, which was positively correlated with the poor prognosis of CC patients. HCP5 knockdown notably restrained CC cell proliferation, colony formation, and migration in vitro, and inhibited tumor growth in vivo. Furthermore, HCP5 can function as the molecular sponge for miR-139-5p to upregulate DNA damage-induced transcript 4 (DDIT4) in CC cells. Murine xenograft studies demonstrated that TGR5 suppressed the tumor formation of CC cells and downregulated HCP5 and DDIT4 while increasing miR-139-5p in the xenografts. Taken together, these findings, for the first time, indicate that TGR5 inhibits CC progression by regulating the HCP5/miR-139-5p/DDIT4 axis, suggesting that it may represent a novel and potent target for CC treatment.

Asunto(s)

Proliferación Celular; Regulación Neoplásica de la Expresión Génica; MicroARNs; ARN Largo no Codificante; Receptores Acoplados a Proteínas G; Neoplasias del Cuello Uterino; Receptores Acoplados a Proteínas G/metabolismo; Receptores Acoplados a Proteínas G/genética; Animales; Humanos; ARN Largo no Codificante/genética; ARN Largo no Codificante/metabolismo; MicroARNs/genética; MicroARNs/metabolismo; Neoplasias del Cuello Uterino/genética; Neoplasias del Cuello Uterino/patología; Neoplasias del Cuello Uterino/metabolismo; Femenino; Ratones; Proliferación Celular/genética; Progresión de la Enfermedad; Ratones Noqueados; Línea Celular Tumoral; Factores de Transcripción/metabolismo; Factores de Transcripción/genética; Movimiento Celular/genética

Palabras clave

HCP5; LncRNA; TGR5; cervical cancer; miRNA

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación Neoplásica de la Expresión Génica / Neoplasias del Cuello Uterino / MicroARNs / Receptores Acoplados a Proteínas G / Proliferación Celular / ARN Largo no Codificante Límite: Animals / Female / Humans Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza

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