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IGFBP7 regulates cell proliferation and migration through JAK/STAT pathway in gastric cancer and is regulated by DNA and RNA methylation.
Mo, Weilie; Deng, Lijian; Cheng, Yun; Ge, Sen; Wang, Jin.
Afiliação
  • Mo W; Department of General Surgery, Changzhou No.7 People's Hospital, Changzhou, China.
  • Deng L; Department of General Surgery, Changzhou Geriatric Hospital affiliated to Soochow University, Changzhou, China.
  • Cheng Y; Department of Oncology, Changzhou No.7 People's Hospital, Changzhou, China.
  • Ge S; Department of Oncology, Changzhou Geriatric Hospital affiliated to Soochow University, Changzhou, China.
  • Wang J; Department of General Surgery, Changzhou No.7 People's Hospital, Changzhou, China.
J Cell Mol Med ; 28(19): e70080, 2024 Oct.
Article em En | MEDLINE | ID: mdl-39351597
ABSTRACT
New biomarkers for early diagnosis of gastric cancer (GC), the second leading cause of cancer-related death, are urgently needed. IGFBP7, known to play various roles in multiple tumours, is complexly regulated across diverse cancer types, as evidenced by our pancancer analysis. Bioinformatics analysis revealed that IGFBP7 expression was related to patient prognosis, tumour clinicopathological characteristics, tumour stemness, microsatellite instability and immune cell infiltration, as well as the expression of oncogenes and immune checkpoints. GSEA links IGFBP7 to several cancer-related pathways. IGFBP7 deficiency inhibited GC cell proliferation and migration in vitro. Furthermore, an in vivo nude mouse model revealed that IGFBP7 downregulation suppressed the tumorigenesis of GC cells. Western blotting analysis showed that the JAK1/2-specific inhibitor ruxolitinib could rescue alterations induced by IGFBP7 overexpression in GC cells. Additionally, our bioinformatics analysis and in vitro assays suggested that IGFBP7 is regulated by DNA methylation at the genetic level and that the RNA m6A demethylase FTO modulates it at the posttranscriptional level. This study emphasizes the clinical relevance of IGFBP7 in GC and its influence on cell proliferation and migration via the JAK/STAT signalling pathway. This study also highlights the regulation of IGFBP7 in GC by DNA and m6A RNA methylation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Gástricas / Transdução de Sinais / Regulação Neoplásica da Expressão Gênica / Movimento Celular / Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina / Metilação de DNA / Proliferação de Células / Fatores de Transcrição STAT Limite: Animals / Female / Humans / Male Idioma: En Revista: J Cell Mol Med Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Gástricas / Transdução de Sinais / Regulação Neoplásica da Expressão Gênica / Movimento Celular / Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina / Metilação de DNA / Proliferação de Células / Fatores de Transcrição STAT Limite: Animals / Female / Humans / Male Idioma: En Revista: J Cell Mol Med Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Reino Unido