Downregulation of microRNA-26a is associated with metastatic potential and the poor prognosis of osteosarcoma patients

• Published in: Oncology reports Vol. 31; no. 3; pp. 1263 - 1270
• Main Authors: SONG, QI-CHUN, SHI, ZHI-BIN, ZHANG, YONG-TAO, JI, LE, WANG, KUN-ZHENG, DUAN, DA-PENG, DANG, XIAO-QIAN
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01-03-2014; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: 3' Untranslated Regions; Analysis; Base Sequence; Binding Sites; Bone cancer; Bone Neoplasms - metabolism; Bone Neoplasms - mortality; Bone Neoplasms - pathology; Cancer therapies; Care and treatment; Cell Line, Tumor; Chemotherapy; Development and progression; Disease-Free Survival; Down-Regulation; Enhancer of Zeste Homolog 2 Protein; EZH2; Female; Gene expression; Gene Expression Regulation, Neoplastic; Genetic aspects; Humans; Kaplan-Meier Estimate; Male; Medical prognosis; Metastasis; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miR-26a; Multivariate Analysis; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - metabolism; Osteosarcoma; Osteosarcoma - metabolism; Osteosarcoma - mortality; Osteosarcoma - secondary; Physiological aspects; Polycomb Repressive Complex 2 - genetics; Polycomb Repressive Complex 2 - metabolism; Prognosis; Radiation therapy; Risk factors; RNA Interference; Sarcoma; Studies; Surgery; Survival analysis; Tumors; China
• ISSN: 1021-335X; 1791-2431
• DOI: 10.3892/or.2014.2989

Accumulating evidence indicates that microRNAs are involved in multiple processes in cancer development and progression. microRNA-26a (miR-26a) has been identified as a tumor suppressor and its downregulation is associated with poor prognosis in several types of human cancer. However, the specific function of miR-26a in osteosarcoma remains unclear. In the present study, we found that the expression of miR-26a in osteosarcoma tissues and cell lines was much lower than that in the normal controls, respectively. In addition, downregulation of miR-26a more frequently occurred in osteosarcoma specimens with adverse clinical stage and with the presence of distant metastasis. Moreover, multivariate survival analyses demonstrated that loss of miR-26a is an independent prognostic factor for both disease-free and overall survival in osteosarcoma. In addition, restoration of miR-26a expression inhibited the invasion and migration in osteosarcoma cells, and miR-26a directly inhibited enhancer of zeste homolog 2 (EZH2) expression by targeting its 3′-UTR. Moreover, EZH2 was upregulated and inversely correlated with miR-26a expression in the osteosarcoma tissues. Thus, for the first time, we provide convincing evidence that downregulation of miR-26a is associated with tumor aggressiveness and tumor metastasis, and miR-26a inhibits cell migration and invasion by targeting the EZH2 gene in osteosarcoma. Thus, miR-26a is an independent prognostic marker for osteosarcoma patients.