[HTML][HTML] MicroRNA-21 in cancer-associated fibroblasts supports lung adenocarcinoma progression

A Kunita, S Morita, TU Irisa, A Goto, T Niki, D Takai… - Scientific reports, 2018 - nature.com
A Kunita, S Morita, TU Irisa, A Goto, T Niki, D Takai, J Nakajima, M Fukayama
Scientific reports, 2018nature.com
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; …
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.
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