MicroRNA-150 functions as a tumor suppressor and sensitizes osteosarcoma to doxorubicin-induced apoptosis by targeting RUNX2

被引:13
作者
Ling, Zhonghua [1 ]
Fan, Gentao [1 ]
Yao, Danhua [1 ]
Zhao, Jianning [1 ]
Zhou, Yinhua [1 ]
Feng, Jinzhu [1 ]
Zhou, Guangxin [1 ]
Chen, Yong [1 ]
机构
[1] Jinling Hosp, Dept Orthoped, 305 Zhongshan East Rd, Nanjing 210002, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
osteosarcoma; microRNA-150; runt-related transcription factor 2; proliferation; chemotherapy; EXPRESSION; PROLIFERATION; PROGRESSION; MIGRATION; PROGNOSIS; INVASION; TXNIP;
D O I
10.3892/etm.2019.8231
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Osteosarcoma (OS) is the most common form of bone malignancy in children and adolescents. MicroRNAs (miRNAs) have been associated with the development and progression of OS. In the present study, reverse transcription-quantitative PCR, western blotting, Cell Counting Kit-8, luciferase and Transwell assays were performed to investigate the biological function of microRNA-150 (miR-150) in OS. The results revealed that miR-150 was significantly downregulated in OS cell lines (HOS, SAOS2, MG-63 and U2OS) in comparison with the normal osteoblast cells (hFOB1.19). Overexpression of miR-150 significantly inhibited cell proliferation in OS cells. miR-150 could sensitize OS cells to chemotherapy treatment of doxorubicin. Runt-related transcription factor 2 (RUNX2) was identified as a target gene of miR-150. RUNX2 knockdown exhibited similar inhibitory effects on both OS cell proliferation and chemotherapy sensitivity. Restoration of RUNX2 reversed the biological function of miR-150. Finally, miR-150 overexpression and RUNX2 knockdown enhanced caspase-3 cleavage. Taken together, the present study established a novel molecular mechanism, in that miR-150 plays tumor suppressor and chemoprotective roles by targeting RUNX2 in OS, indicating that miR-150 may be a potential therapeutic target for OS therapy in the future.
引用
收藏
页码:481 / 488
页数:8
相关论文
共 33 条
[1]   Neoadjuvant chemotherapy for osteosarcoma of the extremities with metastases at presentation: recent experience at the Rizzoli Institute in 57 patients treated with cisplatin, doxorubicin, and a high dose of methotrexate and ifosfamide [J].
Bacci, G ;
Briccoli, A ;
Rocca, M ;
Ferrari, S ;
Donati, D ;
Longhi, A ;
Bertoni, F ;
Bacchini, P ;
Giacomini, S ;
Forni, C ;
Manfrini, M ;
Galletti, S .
ANNALS OF ONCOLOGY, 2003, 14 (07) :1126-1134
[2]   Osteosarcoma: The same old drugs or more? [J].
Bielack, Stefan S. ;
Marina, Neyssa ;
Ferrari, Stefano ;
Helman, Lee J. ;
Smeland, Sigbjorn ;
Whelan, Jeremy S. ;
Reaman, Gregory H. .
JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (18) :3102-3103
[3]   miR-150-5p suppresses tumor progression by targeting VEGFA in colorectal cancer [J].
Chen, Xiaoxiang ;
Xu, Xueni ;
Pan, Bei ;
Zeng, Kaixuan ;
Xu, Mu ;
Liu, Xiangxiang ;
He, Bangshun ;
Pan, Yuqin ;
Sun, Huiling ;
Wang, Shukui .
AGING-US, 2018, 10 (11) :3421-3437
[4]   SWAP70, Actin-Binding Protein, Function as an Oncogene Targeting Tumor-Suppressive miR-145 in Prostate Cancer [J].
Chiyomaru, Takeshi ;
Tatarano, Shuichi ;
Kawakami, Kazumori ;
Enokida, Hideki ;
Yoshino, Hirofumi ;
Nohata, Nijiro ;
Fuse, Miki ;
Seki, Naohiko ;
Nakagawa, Masayuki .
PROSTATE, 2011, 71 (14) :1559-1567
[5]  
Dreyer F, 2016, METHODS MOL BIOL, V1448, P201, DOI 10.1007/978-1-4939-3753-0_15
[6]   Oncomirs - microRNAs with a role in cancer [J].
Esquela-Kerscher, A ;
Slack, FJ .
NATURE REVIEWS CANCER, 2006, 6 (04) :259-269
[7]   Thioredoxin-interacting Protein (Txnip) Is a Feedback Regulator of S-Nitrosylation [J].
Forrester, Michael T. ;
Seth, Divya ;
Hausladen, Alfred ;
Eyler, Christine E. ;
Foster, Matthew W. ;
Matsumoto, Akio ;
Benhar, Moran ;
Marshall, Harvey E. ;
Stamler, Jonathan S. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (52) :36160-36166
[8]   TNF-α's Effects on Proliferation and Apoptosis in Human Mesenchymal Stem Cells Depend on RUNX2 Expression [J].
Ghali, Olfa ;
Chauveau, Christophe ;
Hardouin, Pierre ;
Broux, Odile ;
Devedjian, Jean-Christophe .
JOURNAL OF BONE AND MINERAL RESEARCH, 2010, 25 (07) :1616-1626
[9]   Osteosarcoma [J].
Gorlick, Richard ;
Khanna, Chand .
JOURNAL OF BONE AND MINERAL RESEARCH, 2010, 25 (04) :683-691
[10]   Upregulated circRNA ARHGAP10 Predicts an Unfavorable Prognosis in NSCLC through Regulation of the miR-150-5p/GLUT-1 Axis [J].
Jin, Mingming ;
Shi, Chunzi ;
Yang, Chen ;
Liu, Jianjun ;
Huang, Gang .
MOLECULAR THERAPY-NUCLEIC ACIDS, 2019, 18 :219-231