LncRNA UCA1 maintains the low-tumorigenic and nonmetastatic status by stabilizing E-cadherin in primary prostate cancer cells
LncRNA UCA1 maintains the low-tumorigenic and nonmetastatic status by stabilizing E-cadherin in primary prostate cancer cells
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LncRNA UCA1 通过稳定原发性前列腺癌细胞中的 E-钙粘蛋白来维持低致瘤性和非转移状态
DOI：
10.1002/mc.23247
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发表时间：
2020
影响因子：
4.6
通讯作者：
Yu Jianxiu
中科院分区：
文献类型：
--
作者：
Zhao Xian;Wang Yanli;He Jianfeng;Deng Rong;Huang Xiaojun;Guo Yanmin;Li Lian;Xie Ruiyu;Yu Jianxiu
长非编码RNA(LncRNAs)已经成为癌症生物学中的重要角色。越来越多的证据表明，在癌症中，lncRNAs经常处于失调状态，可能作为癌基因或肿瘤抑制基因发挥作用。尿路上皮癌相关基因1(UCA1)是最先在膀胱移行细胞癌中发现的一种核糖核酸(LncRNA)，在许多不同类型的人类肿瘤中似乎是一种癌基因，通过促进细胞增殖和迁移而发挥作用。在这项研究中，我们揭示了UCA1的一个新的生物学功能，它不同于以往报道的功能，负责维持原代前列腺上皮细胞的低致瘤性和非转移性表型。UCA1通过阻止E-钙粘蛋白与其E3连接酶MDM2的相互作用来稳定E-钙粘素蛋白，从而抑制MDM2介导的泛素化和E-钙粘蛋白的降解。此外，我们还发现UCA1作为miR-296-3p的海绵，在转录后水平靶向E-钙粘素基因CDH1信使RNA。综上所述，这些发现表明，UCA1具有新的重要作用，通过双重机制有效地维持E-钙粘附素的高水平，使原代前列腺癌细胞处于低成瘤和非转移状态。
Long noncoding RNAs (LncRNAs) have emerged as important players in cancer biology. Increasing evidence suggests that LncRNAs are frequently dysregulated in cancer and may function as oncogenes or tumor suppressors. Urothelial carcinoma associated 1 (UCA1), a LncRNA, firstly identified in bladder transitional cell carcinoma, seems to act as an oncogene in many different types of human cancers by promoting cell proliferation and migration. In this study, we revealed a novel biological function of UCA1, which was different from that reported by previous studies, was responsible for maintaining the low‐tumorigenic, nonmetastatic phenotypes in primary prostate epithelial cells. UCA1 could stabilize E‐cadherin protein by preventing the interaction between E‐cadherin and its E3 ligase MDM2, which suppressed MDM2‐mediated ubiquitination and degradation of E‐cadherin. In addition, we also found that UCA1 acted as a sponge of miR‐296‐3p, which targeted E‐cadherin geneCDH1messenger RNA at the posttranscription level. Taken together, these findings demonstrated that UCA1 had a new important role in effectively keeping E‐cadherin at a high level through a dual mechanism, which maintained primary prostate cancer cells at the low‐tumorigenic and nonmetastatic status.