Poster Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Construction of miRNA-RNA networks underlying Taiwanese colorectal cancer for novel targets of therapy and precision medicine (#662)

Hsuan Liu 1 2 3 4 5 , Pei-Ting Hsu 5 , Yi-Shiuan Lai 3
  1. Molecular Medicine Research Center, Chang Gung University, Taoyuan, Guishan, Taiwan
  2. Chang Gung University, Tao-Yuan, Taiwan
  3. Department of Cell and Molecular Biology, Chang Gung University, Taoyuan, Guishan, Taiwan
  4. Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Linkou, Taipei new city, Taiwan
  5. Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Guishan, Taiwan

With growing cancer omics data, the complete functional genomic regulatory network of cancer has been progressively constructed, leading to many new breakthroughs in cancer treatment. Although numerous studies have identified microRNAs as tumor markers, the complete regulatory network and molecular mechanism of their actions is still fragmented, with many key clinical questions concerning treatment and patient outcome still unresolved. This project therefore aims to employ a comprehensive and systematics approach to demarcate and identify novel miRNA-mRNA gene regulatory network and further provide an in-depth understanding of their molecular actions and pathological mechanisms. In the first part, relying on our in-house colorectal cancer mRNA and small RNA sequencing data of 104 pairs of Taiwanese colorectal cancer (CRC) samples, we performed a miRNA-mRNA regulation network analysis to comparatively profile distinctions between tumors and matched normal tissues. After integration with the public TCGA CRC database, we identified two novel miRNAs, which were significantly up-regulated in Taiwanese CRC specimens but conversely down-regulated in the U.S.-based TCGA dataset. We also validated their tumor-associated expression profiles in a second independent clinical cohort. Functionally, cell-based studies showed that these miRNAs exert significant effect on the growth, migration, and invasiveness of CRC tumor cells. In addition, through NGS-based RNA-sequencing and bioinformatics analysis, several potential target genes of these miRNAs and the associated regulatory networks were delineated. Using gene expression and proteomics-based analyses, we further showed that these miRNAs would negatively regulate the expression of several cell cycle- and migration-related genes and proteins. Viewed together, our study provides support to an ethnic basis of CRC tumorigenesis and further uncovers two novel miRNA biomarkers with functional and translational implications.