Common Deregulation of Seven Biological Processes by MicroRNAs in Gastrointestinal Cancers
| Autor: | Matthew T. V. Chan, Lin Zhang, Priscilla T. Y. Law, William K.K. Wu, Yuchen Zhang, Jun Yu, Shan Zhao, Sunny H. Wong |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell signaling Colorectal cancer media_common.quotation_subject Systems biology lcsh:Medicine Biology Endocytosis Article 03 medical and health sciences Epidermal growth factor Cell Line Tumor microRNA medicine Humans lcsh:Science Internalization Gastrointestinal Neoplasms media_common Multidisciplinary Epidermal Growth Factor Genome Human Systems Biology lcsh:R medicine.disease ErbB Receptors Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology Cancer research lcsh:Q Signal transduction Algorithms Signal Transduction |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-11 (2018) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-21573-w |
| Popis: | MicroRNAs are frequently dysregulated in human neoplasms, including gastrointestinal cancers. Nevertheless, the global influence of microRNA dysregulation on cellular signaling is still unknown. Here we sought to elucidate cellular signaling dysregulation by microRNAs in gastrointestinal cancers at the systems biology level followed by experimental validation. Signature dysregulated microRNAs in gastric, colorectal and liver cancers were defined based on our previous studies. Targets of signature dysregulated miRNAs were predicted using multiple computer algorithms followed by gene enrichment analysis to identify biological processes perturbed by dysregulated microRNAs. Effects of microRNAs on endocytosis were measured by epidermal growth factor (EGF) internalization assay. Our analysis revealed that, aside from well-established cancer-related signaling pathways, several novel pathways, including axon guidance, neurotrophin/nerve growth factor signaling, and endocytosis, were found to be involved in the pathogenesis of gastrointestinal cancers. The regulation of EGF receptor (EGFR) endocytosis by two predicted miRNAs, namely miR-17 and miR-145, was confirmed experimentally. Functionally, miR-145, which blocked EGFR endocytosis, prolonged EGFR membrane signaling and altered responsiveness of colon cancer cells to EGFR-targeting drugs. In conclusion, our analysis depicts a comprehensive picture of cellular signaling dysregulation, including endocytosis, by microRNAs in gastrointestinal cancers. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|