Your browser doesn't support javascript.
loading
Pancreatic stellate cells derived exosomal miR-5703 promotes pancreatic cancer by downregulating CMTM4 and activating PI3K/Akt pathway.
Li, Mingzhe; Guo, Huahu; Wang, Qi; Chen, Kai; Marko, Kornmann; Tian, Xiaodong; Yang, Yinmo.
Afiliação
  • Li M; Department of General Surgery, Peking University First Hospital, Beijing, 100034, China. Electronic address: lmzhe@bjmu.edu.cn.
  • Guo H; Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. Electronic address: 1611110217@bjmu.edu.cn.
  • Wang Q; Department of General Surgery, Peking University First Hospital, Beijing, 100034, China. Electronic address: wanglian19920924@pku.edu.cn.
  • Chen K; Department of General Surgery, Peking University First Hospital, Beijing, 100034, China. Electronic address: CK@bjmu.edu.cn.
  • Marko K; Clinic of General, Visceral and Transplantation Surgery, University of Ulm, Ulm, 89081, Germany. Electronic address: marko.kornmann@uniklinik-ulm.de.
  • Tian X; Department of General Surgery, Peking University First Hospital, Beijing, 100034, China. Electronic address: tianxiaodong@pkufh.com.
  • Yang Y; Department of General Surgery, Peking University First Hospital, Beijing, 100034, China. Electronic address: yangyinmosci@163.com.
Cancer Lett ; 490: 20-30, 2020 10 10.
Article em En | MEDLINE | ID: mdl-32585413
Exosomes play important role in tumor microenvironment, and mediate the crosstalk between pancreatic cancer (PC) cells and matrix components including pancreatic stellate cells (PSCs) to regulate pancreatic cancer progression. Here we isolated primary PSCs from PC patients, and demonstrated that PSC-derived exosomes could be internalized by PC cells to promote cell proliferation. Furthermore, we identified that miR-5703 in the exosomes acted as a driver of cell proliferation and its inhibitor suppressed the function of exosomes to promote PC cell proliferation. miR-5703 directly bound to the 3'UTR of CMTM4 and downregulated its expression. CMTM4 knockdown promoted PC cell proliferation, while overexpression of CMTM4 suppressed PC cell proliferation both in vivo and in vitro. Mechanistically, we revealed that CMTM4 suppressed PI3K/Akt pathway via downregulating PAK4. In conclusion, our results suggest that PSC-derived exosomal miR-5703 could target CMTM4 in PC cells and promote cell proliferation due to PAK4 activated PI3K/Akt pathway.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Regulação Neoplásica da Expressão Gênica / Carcinoma Ductal Pancreático / MicroRNAs / Células Estreladas do Pâncreas / Proteínas com Domínio MARVEL Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Regulação Neoplásica da Expressão Gênica / Carcinoma Ductal Pancreático / MicroRNAs / Células Estreladas do Pâncreas / Proteínas com Domínio MARVEL Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article