SP1/AKT/FOXO3 Signaling Is Involved in miR-362-3p-Mediated Inhibition of Cell-Cycle Pathway and EMT Progression in Renal Cell Carcinoma

SP1/AKT/FOXO3 Signaling Is Involved in miR-362-3p-Mediated Inhibition of Cell-Cycle Pathway and EMT Progression in Renal Cell Carcinoma
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SP1/AKT/FOXO3 信号转导参与 miR-362-3p 介导的肾细胞癌细胞周期途径和 EMT 进展的抑制

DOI:
10.3389/fcell.2020.00297
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发表时间:
2020-05
影响因子:
5.5
通讯作者:
Xu Xin
Xu Xin
中科院分区:
生物学2区
文献类型:
--
作者:
Zhu Hejia;Wang Song;Shen Haixiang;Zheng Xiangyi;Xu Xin

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新出现的证据表明,miR-362- 3 p的失调参与了几种类型的人类癌症的发生和发展。然而,miR-362- 3 p在肾细胞癌(RCC)中的作用机制尚不完全清楚。在这项研究中,我们发现miR-362- 3 p在人类RCC组织中频繁下调。RCC细胞中miR-362- 3 p的过表达通过调节AKT/FOXO 3信号通路显着抑制体外和体内的增殖、细胞周期和运动性。我们进一步证实SP1是miR-362- 3 p的直接靶点。通过小干扰RNA(siRNA)敲低SP1表达表型模仿了RCC细胞中miR-362- 3 p过表达的作用。总之,目前的研究结果为miR-362- 3 p在RCC发病机制中的作用提供了证据,因此miR-362- 3 p可能成为RCC治疗的有吸引力的候选者。
Emerging evidence has indicated that dysregulation of miR-362-3p is involved in the initiation and progression of several types of human cancers. However, the molecular mechanism of miR-362-3p in renal cell carcinoma (RCC) is still not completely clear. In this study, we found that miR-362-3p was frequently down-regulated in human RCC tissues. Overexpression of miR-362-3p in RCC cells significantly suppressed the proliferation, cell cycle and motility in vitro and in vivo via regulating AKT/FOXO3 signaling. We further confirmed that SP1 was a direct target of miR-362-3p. Knockdown of SP1 expression by a small interfering RNA (siRNA) phenocopied the effect of miR-362-3p overexpression in RCC cells. In conclusion, the current results provide evidence for the role of miR-362-3p in the pathogenesis of RCC and thus miR-362-3p may serve as an attractive candidate for RCC therapy.
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