DNA methylation mediated repression of miR-886-3p predicts poor outcome of human small cell lung cancer
Menée sur des échantillons tumoraux prélevés sur 82 patients chinois atteints d'un cancer du poumon à petites cellules, puis in vitro et in vivo, cette étude met en évidence une association entre un faible niveau d'expression du micro-ARN 886-3p et un pronostic défavorable
Small-cell lung cancer (SCLC) is one of the most aggressive types of cancer, yet the pathological mechanisms underlying its devastating clinic outcome remain elusive. In this report, we surveyed 924 microRNA (miR) for their expressions in the formalin-fixed paraffin-embedded (FFPE) specimens from 42 SCLC patients, and found that the down-regulated miR-886-3p is closely correlated with the shorter survival of SCLC. This correlation was validated with another 40 cases. It was further discovered that loss of miR-886-3p expression was mediated by DNA hypermethylation of its promoter in both cultured SCLC cells and tumor samples. Moreover, miR-886-3p potently repressed cell proliferation, migration and invasion of NCI-H446 cell in cell culture via suppression of the expression of its target genes: PLK1 and TGF-β1 at post-transcription levels. Forced upregulation of miR-886-3p greatly inhibited in vivo tumor growth, bone/muscle invasion and lung metastasis of NCI-H446 cells. This newly identified miR-886-3p-PLK1 /TGF-β1 nexus that modulates SCLC aggression suggests that both loss of miR-886-3p expression and hypermethylation of the miR-886 promoter are the promising indicators for poor outcome of as well as new therapeutic targets for SCLC.
Cancer Research , résumé, 2013