miR-223-3p Inhibits Human Osteosarcoma Metastasis and Progression by Directly Targeting CDH6.
miR-223-3p Inhibits Human Osteosarcoma Metastasis and Progression by Directly Targeting CDH6.
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miR-223-3p 通过直接靶向 CDH6 抑制人骨肉瘤转移和进展
DOI：
10.1016/j.ymthe.2018.03.009
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发表时间：
2018-05-02
期刊：
影响因子：
--
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Ji Q;Xu X;Song Q;Xu Y;Tai Y;Goodman SB;Bi W;Xu M;Jiao S;Maloney WJ;Wang Y
钙粘蛋白-6（CDH 6）在肿瘤中异常表达，并与肿瘤进展密切相关。然而，CDH 6在人骨肉瘤中的功能和CDH 6在骨肉瘤肿瘤发生中的分子机制仍然知之甚少。在这项工作中，我们评估了CDH 6在人骨肉瘤中的作用，并确定CDH 6的表达与骨肉瘤患者的总体生存率和不良预后密切相关。microRNAs（miRNAs）在骨肉瘤的发生、发展过程中起着重要的表观遗传调节作用。使用双荧光素酶报告基因分析，我们发现miR-223- 3 p通过直接结合CDH 6的3′ UTR来抑制CDH 6的表达。miR-223- 3 p过表达通过抑制体内和体外CDH 6表达显著抑制细胞侵袭、迁移、生长和增殖。此外，CDH 6在miR-223- 3 p转染的骨肉瘤细胞中的过表达有效地挽救了miR-223- 3 p介导的细胞侵袭、迁移、生长和增殖的抑制。此外，Kaplan-Meier分析表明，miR-223- 3 p的表达预测骨肉瘤患者的良好临床结局。此外，miR-223- 3 p在骨肉瘤患者中的表达下调，且与CDH 6的表达呈负相关。总的来说，这些数据强调了miR-223- 3 p/CDH 6轴是一种重要的新型多效性调节因子，可以早期预测人骨肉瘤治疗中的转移潜力。季全波等证明CDH 6与骨肉瘤患者的总体生存和预后相关，并被鉴定为miR-223- 3 p的新的直接靶点。miR-223- 3 p过表达可抑制细胞增殖、侵袭和迁移，提示miR-223- 3 p和CDH 6可能成为骨肉瘤治疗的新的预后生物标志物和治疗靶点。
Cadherin-6 (CDH6) is aberrantly expressed in cancer and closely associated with tumor progression. However, the functions of CDH6 in human osteosarcoma and the molecular mechanisms underlying CDH6 in osteosarcoma oncogenesis remain poorly understood. In this work, we assessed the role of CDH6 in human osteosarcoma and identified that the expression of CDH6 was closely related with the overall survival and poor prognosis of osteosarcoma patients. MicroRNAs (miRNAs) have been implicated as important epigenetic regulators during the progression of osteosarcoma. Using dual-luciferase reporter assays, we showed that miR-223-3p suppresses CDH6 expression by directly binding to the 3′ UTR of CDH6. miR-223-3p overexpression significantly inhibited cell invasion, migration, growth, and proliferation by suppressing the CDH6 expression in vivo and in vitro. Besides, CDH6 overexpression in the miR-223-3p-transfected osteosarcoma cells effectively rescued the inhibition of cell invasion, migration, growth, and proliferation mediated by miR-223-3p. Additionally, Kaplan-Meier analysis suggests that the expression of miR-223-3p predicts favorable clinical outcomes for osteosarcoma patients. Moreover, the expression of miR-223-3p was downregulated in osteosarcoma patients and was negatively associated with the expression of CDH6. Collectively, these data highlight that miR-223-3p/CDH6 axis is an important novel pleiotropic regulator and could early predict the metastatic potential in human osteosarcoma treatments. Quanbo Ji et al. demonstrate that CDH6 is correlated with the overall survival and prognosis of osteosarcoma patients and identified as a novel direct target of miR-223-3p. miR-223-3p overexpression inhibited cell proliferation, invasion, and migration, indicating miR-223-3p and CDH6 could be novel prognostic biomarkers and therapeutic targets for treating osteosarcoma.
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影响因子：
5.6
作者：
Bertoli G;Cava C;Castiglioni I
通讯作者：
Castiglioni I
RanBP9/TSSC3 复合物通过抑制骨肉瘤中 Src 介导的 Akt 信号传导来协同抑制失巢凋亡抵抗和转移。
影响因子：
9
作者：
Dai H;Lv YF;Yan GN;Meng G;Zhang X;Guo QN
通讯作者：
Guo QN
DOI：
10.1016/j.omtn.2017.06.005
发表时间：
2017-09-15
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Chakraborty C;Sharma AR;Sharma G;Doss CGP;Lee SS
通讯作者：
Lee SS
影响因子：
4.7
作者：
Han, Ruhui;Ji, Xiaoming;Ni, Chunhui
通讯作者：
Ni, Chunhui
影响因子：
12.4
作者：
Chen, Chiu-Ling;Wu, Jaw-Ching;Hu, Yu-Chen
通讯作者：
Hu, Yu-Chen