Forkhead box C1 is targeted by microRNA-133b and promotes cell proliferation and migration in osteosarcoma.

Forkhead box C1 is targeted by microRNA-133b and promotes cell proliferation and migration in osteosarcoma.
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DOI:
10.3892/etm.2017.4870
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发表时间:
2017-10
影响因子:
2.7
通讯作者:
Chen J
Chen J
中科院分区:
医学4区
文献类型:
--
作者:
Deng L;Liu T;Zhang B;Wu H;Zhao J;Chen J

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叉头盒C1 (FOXC1)已被证明在许多恶性肿瘤中作为癌基因,尽管其在骨肉瘤(OS)中的潜在作用机制尚不清楚。本研究评估了FOXC1在OS中的表达及其调控作用。逆转录-定量聚合酶链反应和western blot结果显示,FOXC1在OS组织和细胞系中与邻近非肿瘤组织(P<0.001)和正常人成骨细胞(P<0.01)相比均显著上调。此外,晚期临床分期(III-IV)的OS中FOXC1表达水平明显高于低临床分期(I-II; P<0.001)。FOXC1表达下调可显著降低OS U2OS细胞的增殖和迁移(P<0.01),而FOXC1过表达可显著促进U2OS细胞的增殖和迁移(P<0.01)。此外,FOXC1被鉴定为microRNA (miR)-133b的直接靶点,这是一种在OS中报道的肿瘤抑制miR。在U2OS细胞中,miR-133b可负调控FOXC1蛋白表达(P<0.01),在OS中,miR-133b表达与FOXC1表达呈负相关。综上所述,本研究表明,miR-133b靶向的FOXC1可能促进OS中细胞的增殖和迁移。因此,FOXC1可能是治疗OS的潜在治疗靶点。
Forkhead box C1 (FOXC1) has been demonstrated to act as an oncogene in a number of malignant tumors, though its underlying mechanism of action in osteosarcoma (OS) remains unknown. The present study evaluated the expression and regulatory role of FOXC1 in OS. Reverse transcription-quantitative polymerase chain reaction and western blot data indicated that FOXC1 was significantly upregulated in OS tissues and cell lines when compared with adjacent non-tumor tissues (P<0.001) and normal human osteoblast cells (P<0.01), respectively. Moreover, levels of FOXC1 expression were significantly higher in OS at advanced clinical stage (III–IV) when compared with that at low clinical stage (I–II; P<0.001). Knockdown of FOXC1 expression caused a significant decrease in the proliferation and migration of OS U2OS cells (P<0.01), while overexpression of FOXC1 significantly promoted U2OS cell proliferation and migration (P<0.01), relative to control U2OS cells. Furthermore, FOXC1 was identified as a direct target of microRNA (miR)-133b, a reported tumor-suppressive miR in OS. The protein expression of FOXC1 was negatively regulated by miR-133b in U2OS cells (P<0.01), and miR-133b expression was inversely correlated with FOXC1 expression in OS. In conclusion, the present study demonstrated that FOXC1, targeted by miR-133b, may promote cell proliferation and migration in OS. Thus, FOXC1 may be a potential therapeutic target in the treatment of OS.
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