Abstract 4818: miR-34-AGO-TNRC6A complex transcriptionally up-regulates BLU tumor suppressor via binding of a novel promoter-associated lncRNA in lung cancer

We focused on genes whose expression is induced by miR-34a, a potent tumor suppressor microRNA (miRNA) in lung cancer and many other types of cancer, and sought to elucidate the mechanisms underlying the tumor suppressor function of miR-34a. We found that the miR-34a inhibited the proliferation of lung cancer cells by inducing expression of the BLU(also known as ZMYND10) tumor suppressor. The next-generation sequencing analysis of RNA extracted from lung cancer tissues identified a novel divergent lncRNA expressed from promoter of BLUthat include two predicted miR-34 binding sites. Interestingly, miR-34a failed to induce the BLUtranscription in the mutants lacking these miR-34 binding sites in the lncRNA. In addition, the miR-34-AGO-TNRC6A complex induced transcription of BLUby binding to the lncRNA. This non-canonical miRNA pathway, which induces gene expression via cooperation between an miRNA and promoter-associated lncRNA, is a previously unknown tumor suppression mechanism of miR-34a. Citation Format: Shinichiro Ohno, Keiki Oikawa, Yuichirou Harada, Masahiko Kuroda. miR-34-AGO-TNRC6A complex transcriptionally up-regulates BLU tumor suppressor via binding of a novel promoter-associated lncRNA in lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4818.