1] Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA [2] Department of Biochemistry, University of Mississippi Medical Center, Jackson, MS, USA.
1] Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA [2] Department of Microbiology, University of Mississippi Medical Center, Jackson, MS, USA.
Cell Death Dis. 2014 Jan 23;5(1):e1008. doi: 10.1038/cddis.2013.541.
Functional genomics studies have led to the discovery of a large amount of non-coding RNAs from the human genome; among them are long non-coding RNAs (lncRNAs). Emerging evidence indicates that lncRNAs could have a critical role in the regulation of cellular processes such as cell growth and apoptosis as well as cancer progression and metastasis. As master gene regulators, lncRNAs are capable of forming lncRNA-protein (ribonucleoprotein) complexes to regulate a large number of genes. For example, lincRNA-RoR suppresses p53 in response to DNA damage through interaction with heterogeneous nuclear ribonucleoprotein I (hnRNP I). The present study demonstrates that hnRNP I can also form a functional ribonucleoprotein complex with lncRNA urothelial carcinoma-associated 1 (UCA1) and increase the UCA1 stability. Of interest, the phosphorylated form of hnRNP I, predominantly in the cytoplasm, is responsible for the interaction with UCA1. Moreover, although hnRNP I enhances the translation of p27 (Kip1) through interaction with the 5'-untranslated region (5'-UTR) of p27 mRNAs, the interaction of UCA1 with hnRNP I suppresses the p27 protein level by competitive inhibition. In support of this finding, UCA1 has an oncogenic role in breast cancer both in vitro and in vivo. Finally, we show a negative correlation between p27 and UCA in the breast tumor cancer tissue microarray. Together, our results suggest an important role of UCA1 in breast cancer.
功能基因组学研究导致从人类基因组中发现了大量的非编码 RNA；其中包括长非编码 RNA（lncRNA）。新出现的证据表明，lncRNA 可能在细胞生长和凋亡以及癌症进展和转移等细胞过程的调节中发挥关键作用。作为主基因调控因子，lncRNA 能够形成 lncRNA-蛋白（核糖核蛋白）复合物来调节大量基因。例如，lincRNA-RoR 通过与异质核核糖核蛋白 I（hnRNP I）相互作用来响应 DNA 损伤抑制 p53。本研究表明，hnRNP I 还可以与 lncRNA 尿路上皮癌相关 1（UCA1）形成功能性核糖核蛋白复合物并增加 UCA1 的稳定性。有趣的是，hnRNP I 的磷酸化形式主要在细胞质中，负责与 UCA1 相互作用。此外，尽管 hnRNP I 通过与 p27 mRNA 的 5'-非翻译区（5'-UTR）相互作用增强 p27（Kip1）的翻译，但 UCA1 与 hnRNP I 的相互作用通过竞争性抑制抑制 p27 蛋白水平。支持这一发现，UCA1 在体外和体内均在乳腺癌中具有致癌作用。最后，我们在乳腺癌肿瘤组织微阵列中显示了 p27 和 UCA 之间的负相关。总之，我们的研究结果表明 UCA1 在乳腺癌中具有重要作用。
