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Regulation of the small GTPase Ran by miR-802 modulates proliferation and metastasis in colorectal cancer cells.
British Journal of Cancer ( IF 8.8 ) Pub Date : 2020-03-25 , DOI: 10.1038/s41416-020-0809-7
Xin Wang 1, 2 , Danxiu Li 2 , Lina Sun 3 , Gaofei Shen 1 , Hao Liu 1 , Hao Guo 1 , Minghui Ge 4 , Junrong Liang 1, 2 , Ping Chen 1, 2 , Jinchi Zhou 2 , Tianyu Cao 1 , Qi Wang 1 , Xiaoliang Gao 1 , Mingfu Tong 1, 5 , Sijun Hu 1 , Yongzhan Nie 1 , Daiming Fan 1 , Xin Wang 2 , Xiaodi Zhao 1, 6 , Yuanyuan Lu 1
Affiliation  

Background

The small GTPase Ran is upregulated in multiple cancers and fundamental for cancer cell survival and progression, but its significance and molecular mechanisms in colorectal cancer (CRC) remain elusive.

Methods

Ran expression was detected in CRC cell lines and tumour tissues. In vitro and in vivo functional assays were performed to examine the effects of Ran on cell proliferation and metastasis. The pathways and effectors regulated by Ran were explored by an unbiased screening. Bioinformatics prediction and experimental validation were used to identify the miRNA regulator for Ran.

Results

Ran expression was frequently increased in metastatic CRC cells and tissues, especially in metastatic tissues. The upregulation of Ran correlated with poor CRC patient prognosis. Ran silencing reduced proliferation and metastasis of CRC cells both in vitro and in vivo. Ran regulated the expression of EGFR and activation of ERK and AKT signalling pathways. miR-802 was identified as an upstream regulator of Ran and miR-802 overexpression resulted in antiproliferative and antimetastatic activities.

Conclusion

Our study demonstrates the oncogenic roles and underlying mechanisms of Ran in CRC and the novel miR-802/Ran/EGFR regulatory axis may provide potential biomarkers for the treatment of CRC.



中文翻译:

miR-802对小GTPase Ran的调节可调节结直肠癌细胞的增殖和转移。

背景

小GTPase Ran在多种癌症中上调,是癌细胞存活和发展的基础,但其在大肠癌(CRC)中的意义和分子机制仍然难以捉摸。

方法

在CRC细胞系和肿瘤组织中检测到Ran表达。进行体外和体内功能测定以检查Ran对细胞增殖和转移的影响。通过无偏筛选探索了Ran调控的途径和效应子。使用生物信息学预测和实验验证来确定Ran的miRNA调节剂。

结果

在转移性CRC细胞和组织中,尤其是在转移性组织中,Ran表达经常增加。Ran的上调与CRC患者预后差有关。在体外和体内,Ran沉默均可降低CRC细胞的增殖和转移。Ran调节EGFR的表达以及ERK和AKT信号通路的激活。miR-802被确定为Ran的上游调节剂,miR-802的过表达导致抗增殖和抗转移活性。

结论

我们的研究表明Ran在CRC中的致癌作用和潜在机制,而新型miR-802 / Ran / EGFR调控轴可能为CRC的治疗提供潜在的生物标志物。

更新日期:2020-04-24
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