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N6-methyladenosine-modified microRNA-675 advances the development of gastrointestinal stromal tumors via inhibiting myosin phosphatase targeting protein 1.
Ling, Xiaohua; Wang, Ruifeng; Lin, Luoqiang; Wu, Yuxuan; Cheng, Weipeng.
Afiliación
  • Ling X; Department of Gastroenterology, the Fourth Affiliated Hospital of Harbin Medical University, Yiyuan Street No. 37, Nangang District, Harbin 150001, Heilongjiang, China. Electronic address: lingxh1123@hrbmu.edu.cn.
  • Wang R; Department of Gastroenterology, Beijing Tsinghua Changgung Hospital, Litang Road No. 168, Changping District, Beijing 102200, China.
  • Lin L; Department of General Surgery, the Fourth Affiliated Hospital of Harbin Medical University, Yiyuan Street No. 37, Nangang District, Harbin 150001, Heilongjiang, China.
  • Wu Y; Department of Gastroenterology, the Fourth Affiliated Hospital of Harbin Medical University, Yiyuan Street No. 37, Nangang District, Harbin 150001, Heilongjiang, China.
  • Cheng W; Department of Gastroenterology, the Fourth Affiliated Hospital of Harbin Medical University, Yiyuan Street No. 37, Nangang District, Harbin 150001, Heilongjiang, China.
Genomics ; 115(5): 110704, 2023 09.
Article en En | MEDLINE | ID: mdl-37678441
RNA N6-methyladenosine (m6A) modifications influence gastrointestinal stromal tumors (GISTs) development, but the detailed molecular mechanisms have not been fully studied. Here, microRNA-675 was found to be aberrantly elevated in cancerous tissues and cells of GISTs, compared to the corresponding normal counterparts, and GISTs patients with high-expressed microRNA-675 have worse outcomes. Additional experiments confirmed that silencing of microRNA-675 hindered cell division, mobility and tumorigenesis in vitro and in vivo, whereas triggered apoptotic cell death in GISTs cells. Furthermore, microRNA-675-ablation increased the expression levels of myosin phosphatase targeting protein 1 (MYPT1) to inactivate the tumor-initiating RhoA/NF2/YAP1 signal pathway, and downregulation of MYPT1 recovered the malignant phenotypes in microRNA-675-silenced GISTs cells. In addition, we evidenced that METTL3-mediated m6A modifications were essential for sustaining the stability of microRNA-675, and silencing of METTL3 restrained tumorigenesis of GISTs cells by regulating the microRNA-675/MYPT1 axis. To summarize, theMETTL3/m6A/microRNA-675/MYPT1 axis could be used as novel biomarkers for the diagnosis and treatment of GISTs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: MicroARNs / Tumores del Estroma Gastrointestinal Límite: Humans Idioma: En Revista: Genomics Asunto de la revista: GENETICA Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: MicroARNs / Tumores del Estroma Gastrointestinal Límite: Humans Idioma: En Revista: Genomics Asunto de la revista: GENETICA Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos