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Int. J. Mol. Sci. 2017, 18(1), 222;

mir-660-p53-mir-486 Network: A New Key Regulatory Pathway in Lung Tumorigenesis

Department of Experimental Oncology and Molecular Medicine, Unit of Tumor Genomics, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
These authors contributed equally to this study.
Author to whom correspondence should be addressed.
Academic Editor: Nicoletta Sacchi
Received: 30 September 2016 / Revised: 13 January 2017 / Accepted: 17 January 2017 / Published: 23 January 2017
(This article belongs to the Special Issue Cancer Epigenetics)
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Lung cancer is the most frequent cause of cancer-related death worldwide, with limited therapeutic options and rapid development of drug resistance. MicroRNAs, a class of small non-coding RNAs that control different physiological processes, have been associated with cancer development, as either oncomiRNAs or tumor-suppressor miRNAs. In the present study we investigated the interaction between mir-486-5p and mir-660-5p, two independent tumor-suppressor miRNAs, to assess their possible role and synergistic effect in lung cancer treatment. Our data show that mir-660-5p over-expression in A549 lung cancer cells induced a remarkable increase in mir-486-5p expression level and activity, detected as a reduction of its target gene, p85. mir-486-5p expression was confirmed by microRNA in situ hybridization. mir-660-5p modulated mir-486-5p through the silencing of Mouse Double Minute 2 (MDM2), one of its direct target, and then through p53 stimulation. This regulatory pathway was effective in A549, but not in H1299; therefore, only in the context of a functional p53 protein. Our findings support the conclusion that mir-486-5p is positively regulated by mir-660-5p in lung cancer cell lines, through the mir-660-MDM2-p53 pathway, making mir-660-5p even more interesting for its potential successful use in lung cancer therapy. View Full-Text
Keywords: miRNAs; lung cancer; p53 miRNAs; lung cancer; p53

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Borzi, C.; Calzolari, L.; Centonze, G.; Milione, M.; Sozzi, G.; Fortunato, O. mir-660-p53-mir-486 Network: A New Key Regulatory Pathway in Lung Tumorigenesis. Int. J. Mol. Sci. 2017, 18, 222.

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