MicroRNA-1301 suppresses tumor cell migration and invasion by targeting the p53/UBE4B pathway in multiple human cancer cells

• Published in: Cancer letters Vol. 401; pp. 20 - 32
• Main Authors: Wang, Benfan, Wu, Hong, Chai, Chengsen, Lewis, John, Pichiorri, Flavia, Eisenstat, David D, Pomeroy, Scott L, Leng, Roger P
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 10.08.2017; Elsevier Limited
• Subjects: Apoptosis; Binding sites; Brain cancer; Cell Cycle; Cell migration; Cell Movement; Deoxyribonucleic acid; DNA; DNA Methylation; Ectopic expression; Gene expression; Gene Expression Regulation, Neoplastic; Genomes; HCT116 Cells; Hematology, Oncology and Palliative Medicine; Humans; Invasion; Kinases; Metastases; Metastasis; Methods; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Migration; miRNA; Mutagenesis; Neoplasm Invasiveness; Neoplasms - enzymology; Neoplasms - genetics; Neoplasms - pathology; Neuroblastoma; p53; p53 Protein; Plasmids; Promoter Regions, Genetic; Prostate cancer; Ribonucleic acid; RNA; Rodents; Signal Transduction; Software; Transfection; Tumor cells; Tumor suppressor genes; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumors; UBE4B; Ubiquitin-protein ligase; Ubiquitin-Protein Ligase Complexes - genetics; Ubiquitin-Protein Ligase Complexes - metabolism; Ubiquitination; microRNAs; UBE4B; Migration; Invasion; p53
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2017.04.038

Abstract The p53 protein plays a critical role in preventing tumor development. Although numerous factors have been shown to directly or indirectly regulate p53, the mechanism of how microRNAs (miRNAs) modulate p53 remains unclear. Here, we identified miR-1301, a microRNA that regulates the activity and function of p53, by directly targeting the ubiquitination factor E4B (UBE4B), an E3 and E4 ubiquitin ligase. Notably, ectopic expression of miR-1301 inhibits dissemination and metastasis of tumor cells in a p53-dependent manner. Depletion of miR-1301 downregulates p53 function. Our results reveal that there is an inverse correlation between miR-1301 and UBE4B expression and p53 status in prostate cancer. Furthermore, low miR-1301 expression is often associated with incomplete methylation of its gene in human prostate tumors. Together, our results provide the first report indicating that miR-1301 functions as a tumor suppressor that inhibits tumor cell migration and invasion in multiple human cancer cells by regulating the UBE4B-p53 pathway.