MiR-34a inhibits the proliferation, migration, and invasion of oral squamous cell carcinoma by directly targeting SATB2

MiR-34a inhibits the proliferation, migration, and invasion of oral squamous cell carcinoma by directly targeting SATB2
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DOI:
10.1002/jcp.29363
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发表时间:
2019-10-29
影响因子:
5.6
通讯作者:
Ye, Jin-Hai
Ye, Jin-Hai
中科院分区:
生物学2区
文献类型:
--
作者:
Ge, Xin;Gao, Jie;Ye, Jin-Hai

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在多种癌症中,特殊的富含AT的序列结合蛋白2(SATB2)以其非典型表达促进肿瘤的转移和进展,但在口腔鳞状细胞癌(OSCC)中其内在机制和SATB2的状态仍不清楚。本研究的目的是探讨 SATB2 表达在 OSCC 细胞系和组织样本中 miR-34a 下游靶标中所起的作用。在OSCC中,通过定量实时聚合酶链式反应(q-PCR)测定miR-34a的表达,而用q-PCR和蛋白质印迹分析OSCC细胞系和组织样本中SATB2的表达。进行了 miR-34a 对 OSCC 发生影响的体外和体内研究。作为 miR-34a 的直接靶标,SATB2 通过荧光素酶报告基因测定进行了验证。在 miR-34a 水平较低的情况下,OSCC 中的 SATB2 似乎过度表达。此外,在体外和体内,miR-34a 通过下调 SATB2 表达来抑制迁移、侵袭和细胞生长。 SATB2 是 miR-34a 的直接靶标,通过 miR-34a 的共转染证实了 SATB2-3' UTR-wt 报告基因的荧光素酶表达的降低。总的来说,我们的研究证实了miR-34a在OSCC的侵袭、增殖和迁移中的抑制作用,以SATB2作为其下游靶点发挥潜在的抑癌作用。
In various kinds of carcinomas, the special AT-rich sequence-binding protein 2 (SATB2) with its atypical expression promotes the metastasis and progression of the tumor, though in the oral squamous cell carcinoma (OSCC) its inherent mechanism and the status of SATB2 remain unclear. The role played by the SATB2 expression in the OSCC cell lines and tissue samples in the target of miR-34a downstream is the intended endeavor of this study. In te OSCCs the miR-34a expression was determined by quantitative real-time polymerase chain reaction (q-PCR), while the SATB2 expression in the cell lines and tissue samples in OSCC was analyzed with the q-PCR and the western blot. Studies in both in vitro and in vivo of the effects of miR-34a on the initiation of OSCC were conducted. As a direct target of the miR-34a the SATB2 was verified with the luciferase reporter assay. In cases where the miR-34a levels were low, the SATB2 in OSCCs seemed to be overexpressed. Besides, both in the in vitro and in vivo a suppression of migration, invasion, and cell growth was caused by miR-34a by down regulating the SATB2 expression. The SATB2 being a direct target of miR-34a was confirmed by the cotransfection of miR-34a mimics specifically the decrease in the expression of luciferase of SATB2-3 ' UTR-wt reporter. As a whole, our study confirmed the inhibition of miR-34a in the invasion, proliferation, and migration of the OSCCs, playing a potential tumor suppressor role with SATB2 as its downstream target.