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Cancer-associated fibroblasts derived exosomal LINC01833 promotes the occurrence of non-small cell lung cancer through miR-335-5p -VAPA axis.
Chen, Jie; Sun, Jian-Jun; Ma, Ya-Wen; Zhu, Meng-Qin; Hu, Jing; Lu, Qi-Jue; Cai, Zhi-Gang.
Afiliação
  • Chen J; Naval Medical Center of PLA, Thoracic and Cardiac Surgery, Naval Medical University, Shanghai, China.
  • Sun JJ; Naval Medical Center of PLA, Thoracic and Cardiac Surgery, Naval Medical University, Shanghai, China.
  • Ma YW; Department of Cardiology, Naval Medical Center of PLA, Naval Medical University, Shanghai, China.
  • Zhu MQ; Naval Medical Center of PLA, Thoracic and Cardiac Surgery, Naval Medical University, Shanghai, China.
  • Hu J; Naval Medical Center of PLA, Thoracic and Cardiac Surgery, Naval Medical University, Shanghai, China.
  • Lu QJ; Naval Medical Center of PLA, Thoracic and Cardiac Surgery, Naval Medical University, Shanghai, China.
  • Cai ZG; Naval Medical Center of PLA, Thoracic and Cardiac Surgery, Naval Medical University, Shanghai, China.
J Biochem Mol Toxicol ; 38(9): e23769, 2024 Sep.
Article em En | MEDLINE | ID: mdl-39152098
ABSTRACT
Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment (TME) and can induce functional polarization of tumor macrophages. This study aimed to explore the effect of CAFs-derived exosome LINC01833 on the malignant biological behavior of non-small cell lung cancer (NSCLC) cells and its mechanism. Tumor tissues (n = 3) and adjacent noncancerous tissues (n = 3) were collected from patients with NSCLC, and fibroblasts (CAF, NF) were isolated from the two tissues. Expression of LINC01833/miR-335-5p/VAPA in NSCLC clinical tissues and cell lines was detected by RT-qPCR. Exosomes of CAFs and NFs were isolated by ultracentrifugation. Cell proliferation, migration, invasion, and M2 macrophage polarization were detected by MTT, transwell, wound-healing assay, and flow cytometry assay, while western blot was used to verify the expression of M2 macrophage polarization-related proteins. Tumor volume weight and M2 macrophage polarization were detected by tumor xenografts in nude mice. LINC01833 was highly expressed in NSCLC tumor tissues and cells. Knockdown of LINC01833 exosomes could significantly inhibit proliferation, migration, invasion of NSCLC cells, and M2 macrophage polarization of THP-1 cells, while simultaneous knockdown of miR-335-5p on the above basis could reverse the effect of knockdown of LINC01833. In vivo experiments also indicated that knockdown of LINC01833 exosomes suppressed tumor growth and M2 macrophage polarization. CAF-derived LINC01833 exosomes can promote the proliferation, migration and invasion of NSCLC cells and M2 macrophage polarization by inhibiting miR-335-5p and regulating VAPA activity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / MicroRNAs / Exossomos / RNA Longo não Codificante / Fibroblastos Associados a Câncer / Neoplasias Pulmonares / Camundongos Nus Limite: Animals / Female / Humans / Male Idioma: En Revista: J Biochem Mol Toxicol Assunto da revista: BIOLOGIA MOLECULAR / BIOQUIMICA / TOXICOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / MicroRNAs / Exossomos / RNA Longo não Codificante / Fibroblastos Associados a Câncer / Neoplasias Pulmonares / Camundongos Nus Limite: Animals / Female / Humans / Male Idioma: En Revista: J Biochem Mol Toxicol Assunto da revista: BIOLOGIA MOLECULAR / BIOQUIMICA / TOXICOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Estados Unidos