Comprehensive Profiling of Pathologically Relevant Exosomal Mirnas in Colorectal Cancer (Crc) and Functional Characterization: a Next-Generation Sequencing (Ngs)-Based Approach

Colorectal cancer (CRC) is one of the most common cancers worldwide with about 1 million annual cases. In terms of post-surgery disease progression, the overall 5-year survival rate is greater than 50%; however, the recurrence and metastasis rate is high. Clinical follow-ups and treatment after surgery has therefore become an important but currently insufficient practice, indicating a necessity for more refined and non-invasive detection and diagnostic schemes for this particular disease. With the emergence of exosomes - circulating vesicles loaded with cargo DNAs, RNAs, and proteins - as key marker and mediator of tumor progression, these secreted vesicles has now been considered as viable targets for new treatment and/or diagnosis regimens. This proposal therefore aims to establish an integrated experimental paradigm that will provide a systematic profiling of exosome-associated miRNAs with pathological relevance and furthermore an in-depth understanding of their molecular actions and pathological mechanisms. In the first part, the next-generation sequencing (NGS) platforms, with their high-throughput and sensitive capabilities, will be applied to profile CRC-associated exosomal miRNA/transcriptome alterations in the tumor patient samples. Integrative analyses will delineate the “exosomal miRNA maps” that are associated with this particular malignancy. Next, we will carry out independent verification of these CRC-associated exosomal miRNA signatures using different platforms as well as another cohort of patient samples. Moreover, their clinical significance will be examined in terms of association with distinct stages and outcomes of CRC, recurrence/metastasis, and treatment responses, thus facilitating nucleic acids-based prediction of this cancer type. Finally, we also perform cell biological and animal-based assays to functionally characterize the molecular actions and mechanisms of the identified exosomal miRNAs, particularly focusing on the link to the metastatic capacity of the tumor cells as well as the interaction between tumor and microenvironment. These integrated studies are expected to have tremendous potential for the development of new therapeutic interventions for CRC. More significantly, the design and outcome of our proposed research can be extended to functional characterization of other cancers in general and also to the development of personalized medicine schemes.

Project ID:PC10507-1262
External Project ID:MOST105-2320-B182-017