Protein-coding genes account for only a small part of the human genome whereas the vast majority of transcripts make up the non-coding RNAs including microRNAs and long non-coding RNAs (lncRNAs). Both microRNAs and lncRNAs have been shown to play a critical role in regulation of cellular processes such as cell growth and apoptosis as well as cancer progression and metastasis. As master gene regulators, microRNAs can target a large number of protein-coding genes. However, it remains to be determined whether microRNAs can also target lncRNAs. In the present study, we determined whether miR-21 impacts lncRNA expression. Using lncRNA RT-PCR array carrying 83 human disease related lncRNAs, we showed that miR-21 was capable of repressing the growth arrest specific 5 (GAS5) lncRNA which was previously shown to be involved in growth arrest. This negative regulation between miR-21 and GAS5 was confirmed in breast tumor specimens. Of interest, GAS5 can also repress miR-21 expression. While ectopic expression of GAS5 suppressed, GAS5 siRNAs increased miR-21 expression. Importantly, there was a putative miR-21 binding site in exon 5 of GAS5; deletion of the miR-21 binding site abolished this activity. We further showed that biotin labeled GAS5 RNA probe was able to pull down the RNA-induced silencing complex (RISC) and subsequently identified miR-21 in this GAS5-RISC complex, implying that miR-21 and GAS5 may regulate each other in a way similar to the microRNA-mediated silencing of target mRNAs. Together, these results support the “endogenous competitive RNA” concept that microRNAs may regulate not only protein-coding genes, but also non-coding genes such as GAS5.

Citation Format: Ziqiang Zhang, Yin-yuan Mo. Negative regulation of lncRNA GAS5 by miR-21. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1829. doi:10.1158/1538-7445.AM2013-1829