CircRNA WHSC1 targets the miR-646/NPM1 pathway to promote the development of endometrial cancer
CircRNA WHSC1 targets the miR-646/NPM1 pathway to promote the development of endometrial cancer
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CircRNA WHSC1靶向miR-646/NPM1通路促进子宫内膜癌的发展
DOI：
10.1111/jcmm.15346
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发表时间：
2020-05-07
影响因子：
5.3
通讯作者：
Zhao, Yang
中科院分区：
文献类型：
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作者：
Liu, Yao;Chen, Shuo;Zhao, Yang
环状RNA（circRNA）在人类癌症进展中发挥着重要作用。其高稳定性和组织特异性使circRNA成为临床诊断、治疗和预后的重要分子靶点。然而，circRNA WHSC1在子宫内膜癌中的功能和分子机制尚不清楚。采用PCR检测正常子宫内膜和子宫内膜癌组织中CircWHSC1的表达。分别在子宫内膜癌细胞系HEC-1B或Ishikawa中过表达或敲低circWHSC1，通过细胞功能实验检测circWHSC1对子宫内膜癌细胞的影响。采用裸鼠异种移植模型检测circWHSC1过表达后HEC-1B细胞致瘤的变化。利用生物信息学和双荧光素酶报告基因技术来预测和验证circWHSC1对microRNA的海绵化能力。通过使用蛋白质印迹法检测基因表达变化。子宫内膜癌组织中 CircWHSC1 表达增加。 CircWHSC1过表达促进子宫内膜癌细胞的增殖、迁移和侵袭，并减少细胞凋亡。 CircWHSC1 敲低则产生相反的效果。 CircWHSC1过表达的裸鼠表现出致瘤性增加。生物信息学预测 circWHSC1 与 miR-646 结合，这一点通过荧光素酶报告基因检测得到证实。 miR-646的高表达可以逆转circWHSC1对子宫内膜癌细胞的影响。蛋白质印迹显示，在 circWHSC1 过表达或敲低后，核磷蛋白 1 (NPM1)（miR-646 下游靶标）的水平分别升高或降低。 CircWHSC1 通过海绵 miR-646 和靶向 NPM1 促进子宫内膜癌的发展。
Circular RNAs (circRNAs) play important roles in human cancer progression. Their high stability and tissue specificity make circRNAs important molecular targets for clinical diagnosis, treatment and prognosis. However, the functions and molecular mechanisms of circRNA WHSC1 in endometrial cancer are unknown. CircWHSC1 expression in normal endometrial and endometrial cancer tissues was detected using PCR. Overexpression or knockdown of circWHSC1 in endometrial cancer cell lines HEC-1B or Ishikawa, respectively, cell function experiments were used to detect the impact of circWHSC1 on endometrial cancer cells. A nude mouse xenograft model was used to detect changes in tumorigenesis of HEC-1B cells after circWHSC1 overexpression. Bioinformatics and dual luciferase reporter gene technology were used to predict and validate the sponging ability of circWHSC1 on microRNAs. Gene expression changes were detected by using Western blotting. CircWHSC1 expression was increased in endometrial cancer tissues. CircWHSC1 overexpression promoted the proliferation, migration and invasion of endometrial cancer cells and decreased apoptosis. CircWHSC1 knockdown had the opposite effect. CircWHSC1 overexpressed nude mice showed increased tumorigenicity. Bioinformatics predicted that circWHSC1 binds to miR-646, which was confirmed using luciferase reporter gene assays. High expression of miR-646 could reverse the effect of circWHSC1 on endometrial cancer cells. Western blotting showed increased or decreased levels of nucleophosmin 1 (NPM1), an miR-646 downstream target, after circWHSC1 overexpression or knockdown, respectively. CircWHSC1 promotes endometrial cancer development through sponging miR-646 and targeting NPM1.