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

Cristina Borzi, Linda Calzolari, Giovanni Centonze, Massimo Milione, Gabriella Sozzi, Orazio Fortunato

Research output: Contribution to journalArticle

Abstract

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.
Original languageUndefined/Unknown
JournalInternational Journal of Molecular Sciences
Volume18
Issue number1
DOIs
Publication statusPublished - Jan 1 2017

Keywords

  • lung cancer, miRNAs, p53

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