Downregulation of microRNA-26a is associated with metastatic potential and the poor prognosis of osteosarcoma patients.
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.
Department of Orthopedics, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Qi-Chun
QC
Song
Department of Orthopedics, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Zhi-Bin
ZB
Shi
Department of Orthopedics, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Yong-Tao
YT
Zhang
Department of Orthopedics, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Le
L
Ji
Department of Orthopedics, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Kun-Zheng
KZ
Wang
Department of Orthopedics, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
Da-Peng
DP
Duan
Department of Orthopedics, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Xiao-Qian
XQ
Dang
D020413:3' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites; D001859:Bone Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D015536:Down-Regulation; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D034622:RNA Interference
D020413:3' Untranslated Regions; D000071221:Enhancer of Zeste Homolog 2 Protein; D035683:MicroRNAs; D063151:Polycomb Repressive Complex 2; C528163:MIRN26 microRNA, human; C498409:EZH2 protein, human