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

LncRNA-ZXF1 stabilizes P21 expression in endometrioid endometrial carcinoma by inhibiting ubiquitination-mediated degradation and regulating the miR-378a-3p/PCDHA3 axis.
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LncRNA-ZXF1 通过管理泛素化介导的降解和 miR-378a-3p/PCDHA3 轴来调节子宫内膜样子宫内膜癌中 P21 的表达

DOI:
10.1002/1878-0261.12940
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发表时间:
2022-03
期刊:
影响因子:
6.6
通讯作者:
Jiang J
Jiang J
中科院分区:
医学2区
文献类型:
--
作者:
Kong D;Hou Y;Li W;Ma X;Jiang J

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长链非编码RNA(lncRNAs)对各种恶性肿瘤的生物学过程具有深远影响。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,我们聚焦于lncRNA - ZXF1在子宫内膜癌中的作用和机制。利用生物信息学以及体外和体内实验来探究lncRNA - ZXF1的表达和功能。我们发现lncRNA - ZXF1改变了子宫内膜样腺癌(EEC)细胞的迁移和侵袭能力。此外,我们的结果表明lncRNA - ZXF1调控EEC细胞增殖。这种调控可能通过两种机制实现lncRNA - ZXF1介导的P21表达改变。一种是lncRNA - ZXF1作为miR - 378a - 3p的分子海绵来调控PCDHA3的表达,进而调节P21的表达。另一种是lncRNA - ZXF1通过直接与P21结合抑制CDC20介导的泛素化降解。据我们所知,本研究首次探究了lncRNA - ZXF1在EEC中作为一种肿瘤抑制性lncRNA的功能。lncRNA - ZXF1未来可能成为治疗、诊断和预后的指标。 在本研究中,我们发现lncRNA - ZXF1可能作为一种肿瘤抑制基因来调控子宫内膜样腺癌(EEC)的增殖和侵袭。lncRNA - ZXF1可能通过两种机制改变EEC中P21的表达:通过miR - 378a - 3p/PCDHA3轴调控P21蛋白表达,以及通过直接与P21结合防止其被CDC20介导的泛素降解。
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. In this study, we found that lncRNA‐ZXF1 may act as a tumor suppressor gene to regulate the proliferation and invasion of endometrioid endometrial cancer (EEC). LncRNA‐ZXF1 potentially alters P21 expression in EEC through two mechanisms: by regulating P21 protein expression through the miR‐378a‐3p/PCDHA3 axis and by directly binding to P21 to prevent its CDC20‐mediated ubiquitin degradation.
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