Human

Selecting the available treatment for each cancer patient from genomic context is a core goal of precision medicine, but innovative approaches with mechanism interpretation and improved performance are still highly needed. Through utilizing in vitro chemotherapy response data coupled with gene and miRNA expression profiles, we applied a network-based approach that identified markers not as individual molecules but as functional groups extracted from the integrated transcription factor and miRNA regulatory network.

The double helix is a conformation that genomic DNA usually assumes; under certain conditions, however, guanine-rich DNA sequences can form a four-stranded structure, G-quadruplex, which is found to play a role in regulating gene expression. Indeed, it has been demonstrated that the G-quadruplex formed in the c-MYC promoter suppresses its transcriptional activity. Recent studies suggest that G-quadruplex motifs (GQMs) are enriched in human gene promoters.

Cancer evolves through microevolution where random lesions that provide the biggest advantage to cancer stand out in their frequent occurrence in multiple samples. At the same time, a gene function can be changed by aberration of the corresponding gene or modification of microRNA (miRNA) expression, which attenuates the gene. In a large number of cancer samples, these two mechanisms might be distributed in a coordinated and almost mutually exclusive manner.

Recent emerging studies suggest that a substantial fraction of microRNA (miRNA) genes is likely to form clusters in terms of evolutionary conservation and biological implications, posing a significant challenge for the research community and shifting the bottleneck of scientific discovery from miRNA singletons to miRNA clusters. In addition, the advance in molecular sequencing technique such as next-generation sequencing (NGS) has facilitated researchers to comprehensively characterize miRNAs with low abundance on genome-wide scale in multiple species.