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Ibuprofen promotes p75 neurotrophin receptor expression through modifying promoter methylation and N6-methyladenosine-RNA-methylation in human gastric cancer cells.
Jin, Haifeng; Wu, Zheng; Tan, Bibo; Liu, Zhen; Zu, Zhanfei; Wu, Xiaoyun; Bi, Yuwang; Hu, Xingmao.
Afiliación
  • Jin H; Department of Gastroenterology, The 980th Hospital of the PLA Joint Logistics Support Force (Primary Bethune International Peace Hospital of PLA), Shijiazhuang, Hebei, China.
  • Wu Z; Department of Tumor Immunology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
  • Tan B; Department of General Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
  • Liu Z; Department of Gastroenterology, The 980th Hospital of the PLA Joint Logistics Support Force (Primary Bethune International Peace Hospital of PLA), Shijiazhuang, Hebei, China.
  • Zu Z; Department of Gastroenterology, The 980th Hospital of the PLA Joint Logistics Support Force (Primary Bethune International Peace Hospital of PLA), Shijiazhuang, Hebei, China.
  • Wu X; Department of Gastroenterology, The 980th Hospital of the PLA Joint Logistics Support Force (Primary Bethune International Peace Hospital of PLA), Shijiazhuang, Hebei, China.
  • Bi Y; Information Section, The 980th Hospital of the PLA Joint Logistics Support Force (Primary Bethune International Peace Hospital of PLA).
  • Hu X; Medical Management Office of the Medical Service Bureau of the Joint Logistics Support Force.
Bioengineered ; 13(6): 14595-14604, 2022 06.
Article en En | MEDLINE | ID: mdl-35758042
ABSTRACT
It is acknowledged that nonsteroidal anti-inflammatory drugs (NSAIDs) can participate in various signaling pathways, while information about their epigenetic effects are limited. p75NTR (p75 neurotrophin receptor) can inhibit tumor growth by inducing cell cycle arrest and regulating cell cycle arrest and apoptotic cell death. The expression of p75NTR is influenced by epigenetic roles. We explored the effects of ibuprofen on p75NTR expression and investigated whether promoter methylation and N6-methyladenosine (m6A) RNA methylation regulates this process in human gastric cancer cells (SGC7901 and MKN45). Cell lines were treated with ibuprofen 0, 2.5, 5, 10, 20 µM, and then DNA, RNA, and protein were isolated 24 h later. Expression and promoter methylation of p75NTR were detected by RT-qPCR and Western blot. The levels of m6A-p75NTR were measured by RNA immunoprecipitation. We also used RT-qPCR to determine the levels of m6A-related regulators, METTL3, METTL14, ALKBH5, FTO, YTHDC2, and YTHDF1-3. Ibuprofen attenuated p75NTR promoter methylation (p < 0.01) and increased p75NTR level (p < 0.001). Ibuprofen increased m6A-p53 expression (p < 0.01) by promoting the expression of METTL3 (p < 0.01) and METTL14 (p < 0.05); and increased levels of YTHDF1 (p < 0.001), YTHDF3 (p < 0.001), and YTHDC2 (p < 0.01) that finally reinforced p53 translation (p < 0.01). Therefore, our results present that ibuprofen epigenetically increased p75NTR expression by downregulating promoter methylation and upregulating m6A-RNA-methylation in SGC7901 and MKN45 cells. Our study unveils a novel mechanism for p75NTR regulation by NSAIDs and helps the design of treatment targets.
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Texto completo: 1 Colección: 01-internacional Asunto principal: Neoplasias Gástricas / Adenosina / Ibuprofeno / Receptores de Factor de Crecimiento Nervioso / Metilación de ADN / Metiltransferasas / Proteínas del Tejido Nervioso Límite: Humans Idioma: En Revista: Bioengineered Año: 2022 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Asunto principal: Neoplasias Gástricas / Adenosina / Ibuprofeno / Receptores de Factor de Crecimiento Nervioso / Metilación de ADN / Metiltransferasas / Proteínas del Tejido Nervioso Límite: Humans Idioma: En Revista: Bioengineered Año: 2022 Tipo del documento: Article País de afiliación: China