Discovery and analysis of novel microRNAs playing a role in cancer dormancy

Recurrence after cancer treatment accounts for most cancer-related deaths. Disseminated tumor cells can settle in tissues and organs in a quiescence-like state for years or even decades. These quiescent cells are called dormant cells. Dormant cells, when reactivated, form more aggressive and treatment-resistant tumors. Therefore, study of cancer dormancy is very important from a basic science and a clinical perspective. MicroRNAs (miRNAs) are non-coding RNAs playing crucial roles in gene expression regulation. miRNAs generally interact with the 3' untranslated region (UTR) of the gene their target mRNAs, and lead to their degradation or block their translation (3,4). The role of microRNAs in dormant cancer cell behavior is not clear. In our lab, a Matrigel 3D cell culture system was optimized as an in vitro model of cancer dormancy. To discover new players in cancer dormancy using this system, miRNA Sequencing (miR-Seq), RNA Sequencing (RNA-Seq) and proteomics analyses were performed. Comparison of miRSeq results of actively dividing cancer cells with their dormant counterparts revealed a list of dormancy-associated novel miRNAs. As a result of the genetic manipulation of two novel dormancy microRNAs in cancer cell lines, we demonstrated the importance of the miRNAs for dormant cell behavior. Direct gene targets of the miRNAs playing a role in the dormant phenotype were discovered. Study of dormancy-associated miRNAs will allow a better understanding of molecular pathways of cancer dormancy and contribute to the development of new diagnosis, follow-up, and treatment strategies.