Upregulation of miR-211 Promotes Chondrosarcoma Development via Targeting Tumor Suppressor VHL

被引:9
作者
Chen, Changbao [1 ]
Tian, Aixian [2 ]
Zhou, Hua [3 ]
Zhang, Xiaolin [1 ]
Liu, Zhongjun [3 ]
Ma, Xinlong [1 ]
机构
[1] Tianjin Hosp, Dept Spinal Surg, 406 Jiefang South Rd, Tianjin 300211, Peoples R China
[2] Tianjin Hosp, Dept Orthoped Inst, Tianjin 300211, Peoples R China
[3] Peking Univ, Dept Orthopaed Surg, Hosp 3, Beijing 100191, Peoples R China
关键词
miR-211; chondrosarcoma development; VHL; cell survival; therapeutic target; EXPRESSION; CANCER; THERAPEUTICS; APOPTOSIS; MICRORNA;
D O I
10.2147/OTT.S239887
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Introduction: miR-211 has been demonstrated to be aberrantly expressed and plays a pivotal role in human cancers. However, its expression profiles and potential roles in chondrosarcoma development remain still elusive. This study aims to determine the clinical values and underlying roles of miR-211 in chondrosarcoma. Methods: miR-211 expression was analyzed by qRT-PCR in chondrosarcoma specimens and the matched adjacent non-tumor tissues. The relationships among miR-211 expression, clinico-pathological factors and overall survival were also evaluated. Cell viability, colony formation, migration and invasion were further investigated in chondrosarcoma cells. Potential target of miR-211 was predicted using bioinformatics to delineate the molecular mechanisms. Results: miR-211 was remarkably increased in chondrosarcoma compared with the matched adjacent non-tumor tissues. High miR-211 level was identified as 66.7% in chondrosarcoma specimens, which were significantly associated with histological grade and MSTS stage. miR-211 had significant influences on the prognosis of chondrosarcoma patients. Multivariate analysis demonstrated that miR-211 was an independent prognostic factor for overall survival of chondrosarcoma patients. We also found that overexpression or inhibitor of miR-211 promotes or suppresses chondrosarcoma cell proliferation, migration and invasion, respectively. Mechanistically, miR-211 binds to the 3'-UTR of Von Hippel-Lindau (VHL) and suppresses its expression, while restoration of VHL suppressed the potentiated function of miR-211 on proliferation and invasion of chondrosarcoma cells. Conclusion: miR-211 is identified as a potent oncogenic function in chondrosarcoma development, which can serve as a novel biomarker to predict the survival of chondrosarcoma patients. miR-211 potentiates chondrosarcoma growth via targeting VHL, highlighting a novel attractive target for chondrosarcoma treatment.
引用
收藏
页码:2935 / 2943
页数:9
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