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TCEB2/HIF1A signaling axis promotes chemoresistance in ovarian cancer cells by enhancing glycolysis and angiogenesis.
Deng, Zhuo; Li, Bin; Wang, Wenzhi; Xia, Wei; Zhang, Lu; Chen, Lihong; Jin, Wen.
Afiliación
  • Deng Z; Department of Gynecology, Shaanxi Provincial People's Hospital, Xi'an , 710068, Shaanxi, China.
  • Li B; Department of Gynecology, Shaanxi Provincial People's Hospital, Xi'an , 710068, Shaanxi, China.
  • Wang W; Department of Gynecology, Shaanxi Provincial People's Hospital, Xi'an , 710068, Shaanxi, China.
  • Xia W; Department of Gynecology, Shaanxi Provincial People's Hospital, Xi'an , 710068, Shaanxi, China.
  • Zhang L; Department of Gynecology, Shaanxi Provincial People's Hospital, Xi'an , 710068, Shaanxi, China.
  • Chen L; Department of Gynecology, Shaanxi Provincial People's Hospital, Xi'an , 710068, Shaanxi, China.
  • Jin W; Department of Gynecology, Shaanxi Provincial People's Hospital, Xi'an , 710068, Shaanxi, China. 18602930114@163.com.
Eur J Med Res ; 29(1): 456, 2024 Sep 11.
Article en En | MEDLINE | ID: mdl-39261917
ABSTRACT
Ovarian cancer is an extremely malignant gynaecological tumour with a poor patient prognosis and is often associated with chemoresistance. Thus, exploring new therapeutic approaches to improving tumour chemosensitivity is important. The expression of transcription elongation factor B polypeptide 2 (TCEB2) gene is reportedly upregulated in ovarian cancer tumour tissues with acquired resistance, but the specific mechanism involved in tumour resistance remains unclear. In this study, we found that TCEB2 was abnormally highly expressed in cisplatin-resistant tumour tissues and cells. TCEB2 silencing also inhibited the growth and glycolysis of SKOV-3/cisplatin (DDP) and A2780/DDP cells. We further incubated human umbilical vein endothelial cells (HUVECs) with culture supernatants from cisplatin-resistant cells having TCEB2 knockdown. Results revealed that the migration, invasion, and angiogenesis of HUVECs were significantly inhibited. Online bioinformatics analysis revealed that the hypoxia-inducible factor-1A (HIF-1A) protein may bind to TCEB2, and TCEB2 silencing inhibited SKOV-3/DDP cell growth and glycolysis by downregulating HIF1A expression. Similarly, TCEB2 promoted HUVEC migration, invasion, and angiogenesis by upregulating HIF1A expression. In vivo experiments showed that TCEB2 silencing enhanced the sensitivity of ovarian cancer nude mice to cisplatin and that TCEB2 knockdown inhibited the glycolysis and angiogenesis of tumour cells. Our findings can serve as a reference for treating chemoresistant ovarian cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Transducción de Señal / Cisplatino / Resistencia a Antineoplásicos / Subunidad alfa del Factor 1 Inducible por Hipoxia / Glucólisis / Neovascularización Patológica Límite: Animals / Female / Humans Idioma: En Revista: Eur J Med Res Asunto de la revista: MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Transducción de Señal / Cisplatino / Resistencia a Antineoplásicos / Subunidad alfa del Factor 1 Inducible por Hipoxia / Glucólisis / Neovascularización Patológica Límite: Animals / Female / Humans Idioma: En Revista: Eur J Med Res Asunto de la revista: MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido