RRC ID 55924
著者 Kunita A, Morita S, Irisa TU, Goto A, Niki T, Takai D, Nakajima J, Fukayama M.
タイトル MicroRNA-21 in cancer-associated fibroblasts supports lung adenocarcinoma progression.
ジャーナル Sci Rep
Abstract Cancer-associated fibroblasts (CAFs) interact closely with cancer cells, supporting their growth and invasion. To investigate the role of microRNA-21 (miR-21) in lung adenocarcinoma, and especially in its CAF component, in situ hybridisation was applied to samples from 89 invasive lung adenocarcinoma cases. MiR-21 expression was observed in both cancer cells and CAFs. When the patients were stratified by expression, miR-21 levels in CAFs (n = 9), but not in cancer cells (n = 21), were inversely correlated with patient survival; patients with miR-21high CAFs exhibited lower survival than those with miR-21low CAFs. The underlying mechanism was investigated in vitro. Conditioned medium (CM) from A549 lung cancer cells increased miR-21 expression in MRC-5 and IMR-90 lung fibroblasts through the transforming growth factor-β pathway, and induced CAF-like morphology and migratory capacity. MiR-21 up-regulation in lung fibroblasts induced a novel CAF-secreted protein, calumenin, as well as known CAF markers (periostin, α-smooth muscle actin, and podoplanin). Moreover, CM from the lung fibroblasts increased A549 cell proliferation in a calumenin-dependent manner. Thus, miR-21 expression in lung fibroblasts may trigger fibroblast trans-differentiation into CAFs, supporting cancer progression. Therefore, CAF miR-21 represents a pivotal prognostic marker for this scar-forming cancer of the lungs.
巻・号 8(1)
ページ 8838
公開日 2018-6-11
DOI 10.1038/s41598-018-27128-3
PII 10.1038/s41598-018-27128-3
PMID 29892003
PMC PMC5995955
MeSH A549 Cells Adenocarcinoma of Lung / pathology* Cancer-Associated Fibroblasts / metabolism* Cell Proliferation Disease Progression Epithelial Cells / physiology Humans Lung Neoplasms / pathology* MicroRNAs / metabolism* Neoplasm Staging Survival Analysis Tokyo
IF 4.011
引用数 15
リソース情報
ヒト・動物細胞 A549 MRC-5