Regulation of the small GTPase Ran by miR-802 modulates proliferation and metastasis in colorectal cancer cells
Regulation of the small GTPase Ran by miR-802 modulates proliferation and metastasis in colorectal cancer cells
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miR-802 对小 GTPase Ran 的调节调节结直肠癌细胞的增殖和转移
DOI：
10.1038/s41416-020-0809-7
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发表时间：
2020-03-25
影响因子：
8.8
通讯作者：
Lu, Yuanyuan
中科院分区：
文献类型：
--
作者：
Wang, Xin;Li, Danxiu;Lu, Yuanyuan
小分子GTP酶RAN在多种肿瘤中表达上调，对肿瘤细胞的存活和发展起重要作用，但其在结直肠癌中的作用和分子机制尚不清楚。体外和体内功能检测检测RAN对细胞增殖和转移的影响。通过无偏筛选探索RAN调控的通路和效应器。通过生物信息学预测和实验验证来确定RAN的miRNA调节子。结果Ran在转移性结直肠癌细胞和组织中的表达经常增加，尤其是在转移组织中。RAN表达上调与结直肠癌患者预后不良相关。体内和体外RAN沉默均可降低结直肠癌细胞的增殖和转移。RAN调控EGFR的表达以及ERK和AKT信号通路的激活。MiR-802被认为是RAN的上游调控因子，miR-802过表达导致抗增殖和抗转移活性。结论本研究证实了RAN在结直肠癌中的致癌作用和潜在机制，新的miR-802/RAN/EGFR调节轴可能为结直肠癌的治疗提供潜在的生物标志物。
BackgroundThe 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.MethodsRan 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.ResultsRan 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.ConclusionOur 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.