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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.

Author information

1
Department of Immunology, School of Basic Medical Science, Nanjing University of Chinese Medicine, Nanjing, China.
2
Department of Basic Medical Science, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China.
3
Department of Medical Oncology, Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.
4
Department of Oncology, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang, China.
5
Department of Molecular and Translational Science, Monash University, Melbourne, VIC, Australia.

Abstract

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.

PMID:
27869168
DOI:
10.1038/onc.2016.332
[Indexed for MEDLINE]

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