title: Down-regulation of miR-183 promotes migration and invasion of osteosarcoma by targeting Ezrin.
abstract: Recent studies have emphasized causative links between aberrant microRNA expression patterns and cancer progression. miR-183 is dysregulated in certain types of human cancers. The expression pattern, clinical significance, and biological role of miR-183 in osteosarcoma, however, remain largely undefined. In this paired analysis, we found that miR-183 was markedly down-regulated in osteosarcoma cells and tissues compared with matching normal bone tissues using RT-qPCR. Statistical analyses revealed that the expression levels of miR-183 significantly correlated with lung metastasis as well as with local recurrence of osteosarcoma. miR-183 expression was inversely correlated with Ezrin mRNA and protein expression levels in osteosarcoma cells as well as in a subset of primary osteosarcoma. Ectopically expressed miR-183 inhibited migratory and invasive abilities of osteosarcoma cells, whereas knockdown of endogenous miR-183 significantly enhanced these abilities. Using a luciferase reporter carrying the 3'-untranslated region (3'-UTR) of Ezrin, we identified Ezrin as a direct target of miR-183. Moreover, ectopic expression of Ezrin could significantly rescue miR-183-suppressed migration and invasion. Of interest, suppression of Ezrin by miR-183 caused a reduction of phosphorylated p44/42 (p-p44/42). Finally, suppression of Ezrin by RNAi mimicked miR-183 action in the suppression of migration and invasion, which was associated with down-regulation of p-p44/42. Taken together, these results suggest that as a tumor suppressor miRNA, miR-183 plays an important role in the aggressiveness of osteosarcoma.
authors.affiliation: Department of Pathology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhu
authors.forename: Yupeng
authors.initials: Y
authors.lastname: Feng
authors.forename: Zunfu
authors.initials: Z
authors.lastname: Ke
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yang
authors.forename: Junyi
authors.initials: J
authors.lastname: Zhou
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Huang
authors.forename: Liantang
authors.initials: L
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D012334:RNA, Neoplasm / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000502:physiology; D055815:Young Adult; D000099149:Ezrin
chemical_list: D003598:Cytoskeletal Proteins; D035683:MicroRNAs; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D000099149:Ezrin; C533449:MIRN183 microRNA, human