LncRNA TUG1 promotes cell proliferation and suppresses apoptosis in osteosarcoma by regulating miR-212-3p/FOXA1 axis
LncRNA TUG1 promotes cell proliferation and suppresses apoptosis in osteosarcoma by regulating miR-212-3p/FOXA1 axis
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LncRNA TUG1通过调节miR-212-3p/FOXA1轴促进骨肉瘤细胞增殖并抑制细胞凋亡
DOI：
10.1016/j.biopha.2017.12.004
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发表时间：
2018-01-01
影响因子：
7.5
通讯作者：
Cao, Yanming
中科院分区：
文献类型：
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作者：
Xie, Chuhai;Chen, Binwei;Cao, Yanming
背景：据报道，长链非编码RNA牛磺酸上调基因1（TUG1）在骨肉瘤（OS）发展中可能作为一种癌基因发挥作用。然而，TUG1参与OS进展的潜在分子基础仍有待深入研究。
方法：通过实时定量聚合酶链反应（RT - qPCR）检测OS组织和细胞中TUG1和miR - 212 - 3p的表达。通过集落形成实验、MTT实验、流式细胞术分析、半胱天冬酶 - 3活性测定和蛋白质印迹法检测细胞增殖、凋亡、半胱天冬酶 - 3活性以及BCL2、Bax和叉头框A1（FOXA1）的蛋白水平。利用荧光素酶报告基因实验、RNA免疫沉淀（RIP）实验和RT - qPCR探索TUG1、FOXA1和miR - 212 - 3p之间的相互作用。采用肿瘤异种移植小鼠模型在体内证实TUG1在OS中的生物学作用。
结果：在OS组织和细胞中观察到TUG1和FOXA1表达升高，miR - 212 - 3p表达降低。TUG1敲低抑制OS细胞增殖并促进凋亡。TUG1作为miR - 212 - 3p的竞争性内源RNA（ceRNA）发挥作用，并抑制miR - 212 - 3p的表达。miR - 212 - 3p的抑制逆转了TUG1敲低对OS细胞增殖和凋亡的影响。此外，FOXA1被确定为miR - 212 - 3p的靶标，并且在OS细胞中TUG1通过吸附miR - 212 - 3p作为ceRNA上调FOXA1。FOXA1的上调消除了miR - 212 - 3p对OS细胞增殖和凋亡的影响。
结论：TUG1通过调节miR - 212 - 3p/FOXA1轴促进OS细胞增殖并抑制凋亡。因此，TUG1/miR - 212 - 3p/FOXA1轴可能是OS治疗中有希望的治疗靶点。
Background: LncRNA taurine upregulated gene 1 (TUG1) was reported to act as a possible oncogene in osteosarcoma (OS) development. However, the underlying molecular basis of TUG1 involved in the progression of OS remains to be thoroughly investigated.Methods: The expressions of TUG1 and miR-212-3p in OS tissues and cells were examined by RT-qPCR. Cell proliferation, apoptosis, caspase-3 activity, protein levels of BCL2, Bax, and forkhead box A1 (FOXA1) were detected by colony formation assay, MTT assay, flow cytometry analysis, caspase-3 activity assay, and western blot. Luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RT-qPCR were used to explore the interaction between TUG1, FOXA1 and miR-212-3p. Tumor xenograft mouse model was used to confirm the biological role of TUG in OS in vivo.Results: Elevated TUG1 and FOXA1 expression and reduced miR-212-3p expression were observed in OS tissues and cells. TUG1 knockdown suppressed OS cell proliferation and promoted apoptosis. TUG1 functioned as a ceRNA of miR-212-3p and suppressed miR-212-3p expression. miR-212-3p inhibition reversed the effect of TUG1 knockdown on OS cell proliferation and apoptosis. In addition, FOXA1 was identified as a target of miR-212-3p and TUG1 functioned as a ceRNA to upregulate FOXA1 by sponging miR-212-3p in OS cells. FOXA1 up-regulation abolished the effects of miR-212-3p on OS cell proliferation and apoptosis.Conclusion: TUG1 promoted OS cell proliferation and suppressed apoptosis by regulating the miR-212-3p/FOXA1 axis. Therefore, TUG1/miR-212-3p/FOXA1 axis may be a promising therapeutic target in OS treatment.