LncRNA-ZXF1通过抑制泛素化介导的降解和调节miR-378a-3p/PCDHA3轴来稳定子宫内膜样子宫内膜癌中P21的表达,Molecular Oncology

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LncRNA-ZXF1通过抑制泛素化介导的降解和调节miR-378a-3p/PCDHA3轴来稳定子宫内膜样子宫内膜癌中P21的表达
Molecular Oncology ( IF 5.0 ) Pub Date : 2021-03-09 , DOI: 10.1002/1878-0261.12940
Deshui Kong ₁ , Yixin Hou ₁ , Wenzhi Li ₁ , Xiaohong Ma ₁ , Jie Jiang ₁

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长非编码 RNA (lncRNA) 对各种恶性肿瘤的生物过程具有深远的影响。然而，很少有研究探讨它们在子宫内膜癌中的功能和具体机制。在本研究中，我们重点研究lncRNA-ZXF1在子宫内膜癌中的作用和机制。采用生物信息学和体内外实验探讨lncRNA-ZXF1的表达和功能。我们发现lncRNA-ZXF1改变了子宫内膜样子宫内膜癌（EEC）细胞的迁移和侵袭。此外，我们的结果表明 lncRNA-ZXF1 调节 EEC 细胞增殖。这种调节可能是通过 lncRNA-ZXF1 介导的 P21 表达改变通过两种机制来实现的。一是lncRNA-ZXF1作为miR-378a-3p的分子海绵来调节PCDHA3的表达，进而调节P21的表达。另一个是lncRNA-ZXF1通过直接结合P21来抑制CDC20介导的泛素化降解。据我们所知，这项研究是第一个探索 lncRNA-ZXF1 在 EEC 中作为肿瘤抑制 lncRNA 发挥作用的研究。LncRNA-ZXF1未来可能成为治疗、诊断和预后指标。

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LncRNA-ZXF1 stabilizes P21 expression in endometrioid endometrial carcinoma by inhibiting ubiquitination-mediated degradation and regulating the miR-378a-3p/PCDHA3 axis

Long noncoding RNAs (lncRNAs) have a profound effect on biological processes in various malignancies. However, few studies have investigated their functions and specific mechanisms in endometrial cancer. In this study, we focused on the role and mechanism of lncRNA-ZXF1 in endometrial cancer. Bioinformatics and in vitro and in vivo experiments were used to explore the expression and function of lncRNA-ZXF1. We found that lncRNA-ZXF1 altered the migration and invasion of endometrioid endometrial cancer (EEC) cells. Furthermore, our results suggest that lncRNA-ZXF1 regulates EEC cell proliferation. This regulation may be achieved by the lncRNA-ZXF1-mediated alteration in the expression of P21 through two mechanisms. One is that lncRNA-ZXF1 functions as a molecular sponge of miR-378a-3p to regulate PCDHA3 expression and then modulate the expression of P21. The other is that lncRNA-ZXF1 inhibits CDC20-mediated degradation of ubiquitination by directly binding to P21. To the best of our knowledge, this study is the first to explore lncRNA-ZXF1 functioning as a tumor-suppressing lncRNA in EEC. LncRNA-ZXF1 may become therapeutic, diagnostic, and prognostic indicator in the future.

更新日期：2021-03-09

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