Long non-coding RNA TUG1 contributes to tumorigenesis of human osteosarcoma by sponging miR-9-5p and regulating POU2F1 expression
Long non-coding RNA TUG1 contributes to tumorigenesis of human osteosarcoma by sponging miR-9-5p and regulating POU2F1 expression
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长非编码RNA TUG1通过海绵miR-9-5p和调节POU2F1表达促进人骨肉瘤的肿瘤发生
DOI：
10.1007/s13277-016-5391-5
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发表时间：
2016-11-01
期刊：
影响因子：
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通讯作者：
Wu, Bo-Yi
中科院分区：
文献类型：
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作者：
Xie, Chu-Hai;Cao, Yan-Ming;Wu, Bo-Yi
最近的研究表明，长链非编码RNA（lncRNA）在肿瘤发生中起着关键作用，包括骨肉瘤。牛磺酸上调的lncRNA基因1（TUG 1）被报道参与骨肉瘤的进展。在此，我们研究了TUG 1在骨肉瘤细胞中的作用及其机制。通过实时定量PCR（qRT-PCR）测量骨肉瘤细胞系和人正常成骨细胞中TUG 1的表达。利用RNA干扰技术研究TUG 1对骨肉瘤细胞的影响。使用生物信息学分析和荧光素酶测定来确定竞争内源性RNA（ceRNA）的机制。我们的数据表明，TUG 1基因敲低抑制细胞增殖和集落形成，并诱导G 0/G1细胞周期阻滞和凋亡，在体内抑制肿瘤生长。此外，我们发现TUG 1作为内源性海绵直接与miR-9- 5 p结合，下调miR-9- 5 p的表达。此外，TUG 1逆转了miR-9- 5 p对骨肉瘤细胞增殖、集落形成、细胞周期阻滞和凋亡的影响，这涉及POU 2类同源框1（POU 2F 1）表达的去抑制。总之，我们的研究阐明了一种新的TUG 1/miR-9- 5 p/POU 2F 1通路，其中TUG 1通过海绵状miR-9- 5 p作为ceRNA，导致POU 2F 1下调，并促进骨肉瘤的肿瘤发生。这些结果可能有助于lncRNA靶向治疗人骨肉瘤。
Recent studies have shown that long non-coding RNAs (lncRNAs) have critical roles in tumorigenesis, including osteosarcoma. The lncRNA taurine-upregulated gene 1 (TUG1) was reported to be involved in the progression of osteosarcoma. Here, we investigated the role of TUG1 in osteosarcoma cells and the underlying mechanism. TUG1 expression was measured in osteosarcoma cell lines and human normal osteoblast cells by quantitative real-time PCR (qRT-PCR). The effects of TUG1 on osteosarcoma cells were studied by RNA interference in vitro and in vivo. The mechanism of competing endogenous RNA (ceRNA) was determined using bioinformatic analysis and luciferase assays. Our data showed that TUG1 knockdown inhibited cell proliferation and colony formation, and induced G0/G1 cell cycle arrest and apoptosis in vitro, and suppressed tumor growth in vivo. Besides, we found that TUG1 acted as an endogenous sponge to directly bind to miR-9-5p and downregulated miR-9-5p expression. Moreover, TUG1 overturned the effect of miR-9-5p on the proliferation, colony formation, cell cycle arrest, and apoptosis in osteosarcoma cells, which involved the derepression of POU class 2 homeobox 1 (POU2F1) expression. In conclusion, our study elucidated a novel TUG1/miR-9-5p/POU2F1 pathway, in which TUG1 acted as a ceRNA by sponging miR-9-5p, leading to downregulation of POU2F1 and facilitating the tumorigenesis of osteosarcoma. These findings may contribute to the lncRNA-targeted therapy for human osteosarcoma.