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Oncogene. 2017 Mar 23;36(12):1631-1643. doi: 10.1038/onc.2016.332. Epub 2016 Nov 21.

miR-127 promotes EMT and stem-like traits in lung cancer through a feed-forward regulatory loop.

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Department of Immunology, School of Basic Medical Science, Nanjing University of Chinese Medicine, Nanjing, China.
Department of Basic Medical Science, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China.
Department of Medical Oncology, Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.
Department of Oncology, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang, China.
Department of Molecular and Translational Science, Monash University, Melbourne, VIC, Australia.


The coordination between cellular differentiation and the mesenchymal/stem transition is essential for both embryo development and neoplasia, suggesting a mechanistic link between these two major processes. In this work we show that miR-127, an embryo-expressing lung miRNA, was prominently induced in lung adenocarcinoma and correlated with poor prognosis. Elevated miR-127 level drove a pronounced shift from the epithelial to the mesenchymal phenotype in cancer cells, and this shift was associated with their acquisition of stem-like traits, increased resistance to the epidermal growth factor receptor inhibitor and tumor-propagating potential. In contrast, antagonizing miR-127 markedly reversed this malignant transition, compromised the stem-like properties and the in vivo tumorigenic capability of cancer cells. Importantly, a regulatory loop involving the inflammatory signals NF-κB, miR-127 and tumor necrosis factor alpha-induced protein 3 was uncovered as a self-reinforcing circuitry that ensured an aggressive transition in lung cancer. Thus, this work identifies a novel molecular mechanism linking stemness, malignancy and inflammation, opening a new avenue for cancer treatment.

[Indexed for MEDLINE]

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