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Runt-related transcription factor 1 promotes apoptosis and inhibits neuroblastoma progression in vitro and in vivo.
Hong, Mei; He, Jing; Li, Duo; Chu, Yuanyuan; Pu, Jiarui; Tong, Qiangsong; Joshi, Harish C; Tang, Shaotao; Li, Shiwang.
Afiliación
  • Hong M; Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • He J; Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Li D; Central Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Chu Y; Central Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Pu J; Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • Tong Q; Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • Joshi HC; Department of Cell Biology, Emory University, Atlanta, GA, USA.
  • Tang S; Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • Li S; Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. shiwang_union@126.com.
J Exp Clin Cancer Res ; 39(1): 52, 2020 Mar 20.
Article en En | MEDLINE | ID: mdl-32197643
ABSTRACT

BACKGROUND:

Runt-related transcription factor 1 (RUNX1) is a heterodimeric transcription factor that binds to the core element of many enhancers and promoters and can accelerate apoptosis in various tumors. However, the regulatory mechanisms underlying RUNX1 expression in neuroblastoma (NB), a highly malignant tumor in childhood, remain largely unclear. In this study, we aimed to assess the role of RUNX1 in NB and to reveal the underlying mechanisms that may contribute to finding a potential therapeutics strategy against NB.

METHODS:

Growth, invasion, metastasis and angiogenesis were assessed using Cell Counting Kit-8 (CCK-8) immunocytochemistry, and studies involving soft agar, cell invasion, tube formation and whole animals. The levels of expression were measured using real-time quantitative PCR for RNA, Western blot and immunostaining analyses for proteins. Luciferase reporter and chromatin immunoprecipitation assays indicated that RUNX1 directly binds within the BIRC5, CSF2RB and NFKBIA promoter regions to facilitate transcription. The level of apoptosis was assessed by determining mitochondrial membrane potential and flow cytometry.

RESULTS:

RUNX1 was highly expressed in ganglioneuroma (GN) and well-differentiated (WD) tissues relative to the poorly differentiated (PD) and undifferentiated (UD) ones. Moreover, RUNX1 effectively reduced cell viability, invasion, metastasis, angiogenesis, and promoted apoptosis in vitro and in vivo. RUNX1 reduced BIRC5 transcription and increased CSF2RB and NFKBIA transcription by directly binding BIRC5, CSF2RB and NFKBIA promoters. In addition, cytotoxic drugs, especially cisplatin, significantly increased RUNX1 expression in NB cells and promoted apoptosis.

CONCLUSIONS:

These data show that RUNX1 is an independent surrogate marker for the progression of NB and it can be used for monitoring NB prognosis during therapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 2_ODS3 / 7_ODS3_muertes_prevenibles_nacidos_ninos Problema de salud: 2_muertes_prevenibles / 7_non_communicable_diseases / 7_nutrition Asunto principal: Subunidad alfa 2 del Factor de Unión al Sitio Principal / Neuroblastoma Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: J Exp Clin Cancer Res Año: 2020 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 2_ODS3 / 7_ODS3_muertes_prevenibles_nacidos_ninos Problema de salud: 2_muertes_prevenibles / 7_non_communicable_diseases / 7_nutrition Asunto principal: Subunidad alfa 2 del Factor de Unión al Sitio Principal / Neuroblastoma Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: J Exp Clin Cancer Res Año: 2020 Tipo del documento: Article País de afiliación: China
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