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CiRS-7 functions as a ceRNA of RAF-1/PIK3CD to promote metastatic progression of oral squamous cell carcinoma via MAPK/AKT signaling pathways.
Experimental Cell Research ( IF 3.7 ) Pub Date : 2020-09-19 , DOI: 10.1016/j.yexcr.2020.112290
Zhichao Dou 1 , Ling Gao 2 , Wenhao Ren 2 , Hao Zhang 3 , Xiaofei Wang 4 , Shaoming Li 2 , Jingjing Zheng 5 , Xinjuan Kong 6 , Peng Chi 1 , Keqian Zhi 2
Affiliation  

Purpose

Recent findings have shown that circRNA dysregulation was involved in the development of many types of cancer. However, our knowledge of circRNA in oral squamous cell carcinoma (OSCC) remains elusive.

Methods

Here, we explored whether ciRS-7 could function as a ceRNA in promoting metastasis of OSCC via regulating miR-7 activity. The expression levels of ciRS-7 and miR-7 were examined in clinical samples and cell lines by qRT-PCR, and the effects of ectopic expression of ciRS-7 and miR-7 on cell proliferation, migration and invasion were assessed in vitro and in vivo. The effects of ciRS-7 on miR-7 activity were investigated by means of luciferase reporter assay, qRT-PCR and Western blot. In addition, the effects of miR-7 mediated ciRS-7 on the levels of MAPK/AKT signaling proteins were evaluated by Western blot.

Results

We found that ciRS-7 was highly expressed in OSCC tissues and cell lines compared with normal counterparts. Ectopic expression of ciRS-7 significantly promoted OSCC cell proliferation, migration and invasion through in vitro and in vivo. Based on bioinformatics analysis, qRT-PCR, Western blot and luciferase reporter assays, we determined that ciRS-7 functioned as a sponge for miR-7, resulting in attenuation of miR-7 targets RAF-1 and PIK3CD, which are core components of the MAPK/AKT signaling pathways. Moreover, miR-7 correlated with perineural and lymphovascular invasion in OSCC patients. Further experiments demonstrated that ciRS-7 overexpression could attenuate the anti-tumor effects of miR-7 on OSCC cells.

Conclusions

Our results suggested that ciRS-7 can interact directly with miR-7, resulting in upregulation of RAF-1/PIK3CD expression and enhancing metastatic progression of OSCC.



中文翻译:

CiRS-7充当RAF-1 / PIK3CD的ceRNA,通过MAPK / AKT信号通路促进口腔鳞状细胞癌的转移进程。

目的

最近的发现表明,circRNA失调参与了许多类型癌症的发展。但是,我们对circRNA在口腔鳞状细胞癌(OSCC)中的了解仍然难以捉摸。

方法

在这里,我们探讨了ciRS-7是否可以通过调节miR-7活性来作为ceRNA促进OSCC转移。通过qRT-PCR检测临床样品和细胞系中ciRS-7和miR-7的表达水平,并在体外评估ciRS-7和miR-7异位表达对细胞增殖,迁移和侵袭的影响。体内。通过荧光素酶报告基因分析,qRT-PCR和Western blot研究了ciRS-7对miR-7活性的影响。另外,通过蛋白质印迹评估了miR-7介导的ciRS-7对MAPK / AKT信号蛋白水平的影响。

结果

我们发现,与正常对应物相比,ciRS-7在OSCC组织和细胞系中高表达。ciRS-7的异位表达通过体外和体内显着促进OSCC细胞增殖,迁移和侵袭。根据生物信息学分析,qRT-PCR,Western印迹和荧光素酶报告基因分析,我们确定ciRS-7充当miR-7的海绵,导致miR-7靶标RAF-1和PIK3CD的衰减,这是该蛋白的核心成分MAPK / AKT信号通路。而且,miR-7与OSCC患者的神经周围和淋巴血管浸润相关。进一步的实验表明,ciRS-7的过表达可以减弱miR-7对OSCC细胞的抗肿瘤作用。

结论

我们的结果表明,ciRS-7可以与miR-7直接相互作用,从而导致RAF-1 / PIK3CD表达上调并增强OSCC的转移进程。

更新日期:2020-10-07
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