MicroRNA-dependent Regulation of Telomere Maintenance Mechanisms: A Field as Much Unexplored as Potentially Promising
Francesca Santambrogio, Paolo Gandellini, Graziella Cimino-Reale, Nadia Zaffaroni and Marco Folini
Affiliation: Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Amadeo, 42 – 20133 Milano, Italy.
Keywords: ALT, cancer, chromosome stability, miRNA, senescence, telomerase, telomeres, therapy.
The activation of telomere maintenance mechanisms, which rely on telomerase reactivation or on a recombination-based process
known as alternative lengthening of telomeres, guarantees a limitless proliferative potential to human tumor cells. To date, the molecular
underpinnings that drive the activation of telomere maintenance mechanisms during tumorigenesis are poorly understood, but
there are indications that complex signaling networks might be involved. Since telomerase activity has been mainly detected in tumors of
epithelial origin and the alternative lengthening of telomere mechanisms is more frequently expressed in mesenchymal and neuroepithelial
cancers, it could be hypothesized that cell-type specific mechanisms can favor their activation during tumor development. In this context,
microRNAs – small non coding RNAs that regulate gene expression at post-transcriptional level - have emerged as key players in
the development and progression of human cancers, being involved in the control of all the typical features of cancer cells, including the
limitless replicative potential. In the present review, we will summarize the recent findings concerning the identification and biological
validation of microRNAs which may play a role in the regulation of telomere biology as well as of the mechanisms that govern telomere
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