研究动态
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PIN1P1 被 CREB1 激活,并通过与 YBX1 相互作用并上调 PIN1 促进胃癌进展。

PIN1P1 is activated by CREB1 and promotes gastric cancer progression via interacting with YBX1 and upregulating PIN1.

发表日期:2023 Nov 06
作者: Ya-Wen Wang, Wen-Jie Zhu, Ran-Ran Ma, Ya-Ru Tian, Xu Chen, Peng Gao
来源: Cellular & Molecular Immunology

摘要:

长非编码RNA (lncRNA) 在癌症的发生和进展中发挥着关键作用。然而,假基因lncRNA PIN1P1在胃癌中的作用和机制仍不清楚。研究lncRNA PIN1P1在胃癌中的表达和作用。通过 ChIP 和荧光素酶测定确定 CREB1 对 PIN1P1 的转录调控。通过 RNA pull-down、RIP 和蛋白质印迹分析进一步探讨了 PIN1P1 在胃癌中的机制模型。 PIN1P1在胃癌组织中过度表达,PIN1P1上调预示患者预后不良。 CREB1直接与PIN1P1的启动子区结合,促进PIN1P1的转录。 CREB1 介导的增殖、迁移和侵袭增强可以通过 PIN1P1 的下调部分逆转。过表达的PIN1P1促进胃癌细胞的增殖、迁移和侵袭,而降低的PIN1P1则表现出相反的作用。 PIN1P1直接与YBX1相互作用并促进YBX1蛋白表达,导致PIN1上调,其中E2F1可能参与其中。在 PIN1P1 过表达期间沉默 YBX1 可以部分挽救 PIN1 上调。 PIN1(PIN1P1 的亲本基因)在胃癌组织中升高,其上调与患者不良预后相关。 PIN1促进胃癌细胞增殖、迁移和侵袭。综上所述,CREB1激活的PIN1P1可以通过YBX1和上调PIN1促进胃癌进展,表明它是胃癌的潜在靶点。© 2023 作者。细胞与分子医学基金会和约翰·威利出版的《细胞与分子医学杂志》
Long noncoding RNAs (lncRNAs) play critical roles in the carcinogenesis and progression of cancers. However, the role and mechanism of the pseudogene lncRNA PIN1P1 in gastric carcinoma remain unclear. The expression and effects of lncRNA PIN1P1 in gastric cancer were investigated. The transcriptional regulation of CREB1 on PIN1P1 was determined by ChIP and luciferase assays. The mechanistic model of PIN1P1 in gastric cancer was further explored by RNA pull-down, RIP and western blot analysis. PIN1P1 was overexpressed in gastric cancer tissues, and upregulated PIN1P1 predicted poor prognosis in patients. CREB1 was directly combined with the promoter region of PIN1P1 to promote the transcription of PIN1P1. CREB1-mediated enhanced proliferation, migration and invasion could be partially reversed by downregulation of PIN1P1. Overexpressed PIN1P1 promoted the proliferation, migration and invasion of gastric cancer cells, whereas decreased PIN1P1 showed the opposite effects. PIN1P1 directly interacted with YBX1 and promoted YBX1 protein expression, leading to upregulation of PIN1, in which E2F1 may be involved. Silencing of YBX1 during PIN1P1 overexpression could partially rescue PIN1 upregulation. PIN1, the parental gene of PIN1P1, was elevated in gastric cancer tissues, and its upregulation was correlated with poor patient outcomes. PIN1 facilitated gastric cancer cell proliferation, migration and invasion. To sum up, CREB1-activated PIN1P1 could promote gastric cancer progression through YBX1 and upregulating PIN1, suggesting that it is a potential target for gastric cancer.© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.