期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 474, 期 4, 页码 730-735出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2016.05.018
关键词
Fibulin-4; MicroRNA-137; Wnt/beta-Catenin; Osteosarcoma
Fibulin-4, an extracellular glycoprotein implicated in connective tissue development and elastic fiber formation, draws increasing focuses in cancer research. However, little is known about the underlying oncogenic roles of Fibulin-4 in human osteosarcoma (OS). In this study, by immunohistochemical analysis, upregulated expression of Fibulin-4 was found in the OS clinical specimens and cell lines compared to their normal counterparts. Fibulin-4 was positively correlated with the T stage of OS patients, and the proliferation index Ki67. Based on informatics analysis and functional verification, microRNA-137 was identified as a potential upstream regulator of Fibulin-4. Knockdown of Fibulin-4 or introduction of microRNA-137 inhibited cell proliferation and promoted cell apoptosis, and adverse effects were observed by overexpression of Fibulin-4. Furthermore, the tumor-suppressive functions of microRNA-137 were markedly abolished by restoration of Fibulin-4 expression in OS cells. Mechanistically, Fibulin-4 activated Wnt/beta-Catenin pathway and promoted the expression of its downstream targets, including CCND2, c-Myc and VEGF. Taken together, Fibulin-4 plays critical neoplastic roles in tumor growth of human OS by activating Wnt/beta-Catenin signaling and may represent a potential therapeutic target. (C) 2016 Elsevier Inc. All rights reserved.
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