Identification of the Roles of microRNAs and
Other Non-Coding RNAs in Cancer Predisposition
Familial cancers represent diseases in which non-coding RNAs have central pathogenetic roles. We hypothesize that previously non-identified, non-coding RNAs with roles in sporadic and familial cancers could be identified by using their genomic association (flagging) with known cancer-associated, single-nucleotide polymorphisms (SNPs). Furthermore, SNPs in interactor sites with microRNAs are involved in cancer predisposition. The genome-wide identification of non-coding RNAs predisposed to cancer would prove a new mechanism of cancer predisposition with clear implications for further molecular screening and diagnosis.
Identification of Non-Coding RNAs Involved in Metastasis
During tumorigenesis, genome-wide abnormalities in both microRNAs and ultraconserved genes (UCGs) occur in a correlated way that results in our hypothesis that dramatic differences occur in the expression of UCGs and miRNAs in non-metastatic versus metastatic cancers. microRNAs have important genes as targets – including known oncogenes and tumor supressors involved in pancreatic invasion and metastasis. Additionally, miRNAs interact directly with and regulate the expression of UCGs and/or, conversely, UCGs can regulate the expression of miRNAs. The transcriptional or post-transcriptional down-regulation of target levels by miRNAs and UCGs may have functional consequences by impairing the cell cycle and the survival, migration and invasion capacity of cancer cells.
Identification of microRNAs and Other Non-Coding RNAs as Diagnostic and Prognostic Markers in Human Cancers
microRNAs as the Oldest Hormones
miRNA levels in the plasma from cancer patients are significantly different than those of non-cancer control individuals. The plasma miRNAs levels from cancer patients correlate with clinical and prognostic parameters and the miRNA quantification from plasma could be included as a new prognostic marker. Furthermore, the identification of traces of specific miRNAs, known to have a pathogenetic effect, could signal the recurrence of disease. Human-specific ncRNAs exist in the genome and are involved in the functional fingerprints that differentiate human cancers from cancers in other organisms. microRNAs are secreted by malignant cells in the microenvironment and uptake directly or through bodily fluids by effector cells.
Development of New Therapeutic Strategies Involving microRNAs and Other Non-Coding RNAs
microRNAs could represent a new family of tumor suppressor or oncogenic targets for cancer gene therapy. The microRNA viral vectors will be released efficiently inside the target cells and induce or block the expression of microRNAs of interest. The microRNA viral vectors will induce apoptosis of malignant cells and the spectrum of altered targets will include protein-coding genes known to be important in human tumorigenesis.