Abstract
Abstract Background: Emerging evidence has implicated long non-coding RNAs (lncRNAs) as master gene regulators; and they are often aberrantly expressed in a variety of human diseases including cancer. One of the mechanisms of lncRNA-mediated gene expression involves modulation of translation or mRNA stability by interacting with RNA binding proteins. We have previously demonstrated that lncRNA-RoR is a strong negative regulator of p53 in response to DNA damage. The present study was to determine whether and how lncRNA-RoR regulates c-Myc in colon cancer. Methods: MTT assays were used to determine cell growth. Colon cancer tissue array was used to determine the level of lncRNA-RoR in colon cancer tissues by qRT-PCR. Interaction between lncRNA-RoR and RNA binding proteins was confirmed by RNA co-immunoprecipitation and RNA precipitation. LncRNA-RoR knockout in colon cancer cells was through CRISPR/Cas9 system. Dual fluorescent in situ hybridization (FISH) was used to determine the relative levels of lncRNA-RoR and c-Myc mRNA, and their co-localizations in colon cancer specimens. The effect of lncRNA-RoR on tumor growth was determined by a xenograft mouse model. Results: Ectopic expression of lncRNA-RoR upregulated, whereas RoR-siRNA inhibited c-Myc mRNA and protein level, which was further confirmed by lncRNA-RoR knockout. Mechanistically, we showed that lncRNA-RoR directly interacted with RNA binding proteins, hnRNP U and hnRNP D, both of which are implicated in stability of c-Myc mRNA. This interaction was further confirmed by RNA immunoprecipitation. In consistent with these findings, ectopic expression of lncRNA-RoR stimulated cell proliferation but knockout of lncRNA-RoR significantly decreased cell proliferation. Moreover, ectopic expression of lncRNA-RoR in HCT-116 cells significantly promoted tumor growth in a xenograft mouse model. Finally, qPCR array showed the significant upregulation of lncRNA-RoR in colon cancer tissues. Similarly dual FISH revealed a strong correlation between lncRNA-RoR and c-Myc mRNA in colon cancer tissues. Conclusion: It is well known that c-Myc mRNA has a very short half-life and regulation of c-Myc mRNA stability is complex. Our results suggest a novel mechanism of regulation of c-Myc mRNA stability involving lncRNA-RoR, hnRNP U and hnRNP D. Citation Format: Jianguo Huang. LncRNA RoR enhances the c-Myc mRNA stability in colon cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 159. doi:10.1158/1538-7445.AM2015-159
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