MiR-133b is down-regulated in human osteosarcoma and inhibits osteosarcoma cells proliferation, migration and invasion, and promotes apoptosis.
MiR-133b is down-regulated in human osteosarcoma and inhibits osteosarcoma cells proliferation, migration and invasion, and promotes apoptosis.
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DOI：
10.1371/journal.pone.0083571
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Zhao H;Li M;Li L;Yang X;Lan G;Zhang Y
MicroRNAs （miRNAs）降低特定靶癌基因或肿瘤抑制基因的表达，因此在肿瘤发生和肿瘤生长中起着至关重要的作用。迄今为止，调节骨肉瘤生长和进展的潜在mirna尚未完全确定。在本研究中，对人骨肉瘤样本进行了miRNA微阵列检测和分层聚类分析。与正常人骨骼肌相比，43个mirna在人骨骼肌中表达显著差异（倍数变化≥2，p≤0.05）。在这些mirna中，miR-133a和miR-133b的表达分别下降了135倍和47倍，在冷冻和石蜡包埋的骨肉瘤样本中都证实了表达的下降。然后将miR-133b前体表达载体转染到骨肉瘤细胞系U2-OS和MG-63中，并用嘌呤霉素选择稳定的转染物。我们发现，在骨肉瘤细胞系U2-OS和MG-63中，miR-133b的稳定过表达抑制了细胞的增殖、侵袭和迁移，并诱导细胞凋亡。此外，过表达miR-133b可降低预测靶基因BCL2L2、MCL-1、IGF1R和MET的表达，以及磷酸化akt和FAK的表达。本研究对骨肉瘤中miRNAs的失调提供了新的认识，并提示miR-133b可能在骨肉瘤中发挥肿瘤抑制基因的作用。
MicroRNAs (miRNAs) decrease the expression of specific target oncogenes or tumor suppressor genes and thereby play crucial roles in tumorigenesis and tumor growth. To date, the potential miRNAs regulating osteosarcoma growth and progression are not fully identified yet. In this study, the miRNA microarray assay and hierarchical clustering analysis were performed in human osteosarcoma samples. In comparison with normal human skeletal muscle, 43 miRNAs were significantly differentially expressed in human osteosarcomas (fold change ≥2 and p≤0.05). Among these miRNAs, miR-133a and miR-133b expression was decreased by 135 folds and 47 folds respectively and the decreased expression was confirmed in both frozen and paraffin-embedded osteosarcoma samples. The miR-133b precursor expression vector was then transfected into osteosarcoma cell lines U2-OS and MG-63, and the stable transfectants were selected by puromycin. We found that stable over-expression of miR-133b in osteosarcoma cell lines U2-OS and MG-63 inhibited cell proliferation, invasion and migration, and induced apoptosis. Further, over-expression of miR-133b decreased the expression of predicted target genes BCL2L2, MCL-1, IGF1R and MET, as well as the expression of phospho-Akt and FAK. This study provides a new insight into miRNAs dysregulation in osteosarcoma, and indicates that miR-133b may play as a tumor suppressor gene in osteosarcoma.
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DOI：
10.1111/j.1440-1746.2008.05666.x
发表时间：
2009-04-01
影响因子：
4.1
作者：
Guo, Junming;Miao, Ying;Wang, Yanjun
通讯作者：
Wang, Yanjun
影响因子：
11.2
作者：
Jones KB;Salah Z;Del Mare S;Galasso M;Gaudio E;Nuovo GJ;Lovat F;LeBlanc K;Palatini J;Randall RL;Volinia S;Stein GS;Croce CM;Lian JB;Aqeilan RI
通讯作者：
Aqeilan RI
影响因子：
3.7
作者：
Ichikawa T;Sato F;Terasawa K;Tsuchiya S;Toi M;Tsujimoto G;Shimizu K
通讯作者：
Shimizu K
影响因子：
37.3
作者：
Bandrés E;Cubedo E;Agirre X;Malumbres R;Zárate R;Ramirez N;Abajo A;Navarro A;Moreno I;Monzó M;García-Foncillas J
通讯作者：
García-Foncillas J
MicroRNA-133a 在骨肉瘤中下调，通过靶向 Bcl-xL 和 Mcl-1 抑制增殖并促进细胞凋亡
影响因子：
4.1
作者：
Ji, Fang;Zhang, Hao;Tang, Hao
通讯作者：
Tang, Hao