Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Faculty of Health of Sciences, Institute of Translational Medicine, University of Macau, Macau SAR, China.
Mol Carcinog. 2020 Oct;59(10):1174-1187. doi: 10.1002/mc.23247. Epub 2020 Aug 17.
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 gene CDH1 messenger 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.
长链非编码 RNA（lncRNAs）已成为癌症生物学中的重要参与者。越来越多的证据表明，lncRNAs 在癌症中经常失调，可能作为癌基因或肿瘤抑制因子发挥作用。尿路上皮癌相关 1（UCA1）是一种 lncRNA，最初在膀胱癌中被鉴定出来，似乎通过促进细胞增殖和迁移，在许多不同类型的人类癌症中发挥癌基因的作用。在这项研究中，我们揭示了 UCA1 的一个新的生物学功能，与之前的研究报道不同，它负责维持原代前列腺上皮细胞的低致瘤性、非转移性表型。UCA1 可以通过阻止 E-钙粘蛋白与其 E3 连接酶 MDM2 之间的相互作用来稳定 E-钙粘蛋白蛋白，从而抑制 MDM2 介导的 E-钙粘蛋白的泛素化和降解。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-钙粘蛋白基因 CDH1 的信使 RNA。总之，这些发现表明，UCA1 通过双重机制在有效地保持 E-钙粘蛋白处于高水平方面发挥了新的重要作用，从而使原代前列腺癌细胞保持低致瘤性和非转移性状态。
