title: miR-135b, a key regulator of malignancy, is linked to poor prognosis in human myxoid liposarcoma.
abstract: Myxoid/round cell (RC) liposarcomas (MLS) were originally classified into two distinct populations based on histological differences; a myxoid component and a RC component. It is notable that, depending on an increase of the RC component, the prognosis significantly differs. Hence, the RC component is associated with metastasis and poor prognosis. However, the molecular mechanisms that contribute to the malignancy of the RC component still remain largely unknown. Here, we report microRNA-135b (miR-135b), a key regulator of the malignancy, highly expressed in the RC component and promoting MLS cell invasion in vitro and metastasis in vivo through the direct suppression of thrombospondin 2 (THBS2). Decreased THBS2 expression by miR-135b increases the total amount of matrix metalloproteinase 2 (MMP2) and influences cellular density and an extracellular matrix structure, thereby resulting in morphological change in tumor. The expression levels of miR-135b and THBS2 significantly correlated with a poor prognosis in MLS patients. Overall, our study reveals that the miR-135b/THBS2/MMP2 axis is tightly related to MLS pathophysiology and has an important clinical implication. This work provides noteworthy evidence for overcoming metastasis and improving patient outcomes, and sheds light on miR-135b and THBS2 as novel molecular targets for diagnosis and therapy in MLS.
authors.affiliation: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.|Department of Orthopaedic Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nezu
authors.affiliation: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hagiwara
authors.affiliation: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Fujiwara
authors.affiliation: Department of Orthopaedic Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Yoshida
authors.affiliation: Division of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kawai
authors.affiliation: Department of Orthopaedic Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.affiliation: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ochiya
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D018208:Liposarcoma, Myxoid / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008175:Lung Neoplasms / Q000556:secondary; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis; D011379:Prognosis; D034622:RNA Interference; D019699:Thrombospondins / Q000235:genetics; D047368:Tumor Burden; D000099262:Thrombospondin 2
chemical_list: D020413:3' Untranslated Regions; D020778:Matrix Metalloproteinase 2; D035683:MicroRNAs; D019699:Thrombospondins; D000099262:Thrombospondin 2; C544965:MIRN135 microRNA, human