Abstract
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.
Highlights
In support of this notion, a number of proteins have been shown to interact with long non-coding RNA (lncRNA)
Previous studies suggest that the 50-untranslated region (UTR) of p53 mRNA may form a secondary structure to serve as an internal ribosome entry site (IRES);[16,17] heterogeneous nuclear ribonucleoprotein I (hnRNP I) is capable of binding to the IRES to stimulate p53 translation
We asked whether hnRNP I can functionally interact with other lncRNAs in addition to RoR
Summary
In support of this notion, a number of proteins have been shown to interact with lncRNAs. As it is highly expressed in bladder transitional cell carcinoma, it was suggested to serve as a biomarker for the diagnosis of bladder cancer Another isoform (2.2 kb) was identified by a different group as cancer upregulated drug resistant (CUDR) gene in the doxorubicinresistant subline of human squamous carcinoma A431 cells.[26] Sequence alignment revealed that the 1.4 isoform is contained in the 2.2 kb isoform. These studies suggest an oncogenic role of UCA1 in bladder cancer, the underlying mechanism is largely unknown. The role of UCA1 in other type of cancers such as breast cancer remains to be determined
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