Abstract
Abstract N6-methyladenosine (m6A) is one of the most prevalent internal modifications in eukaryotic messenger RNA. This dynamic and reversible modification is installed by methyltransferase complex consisting of three subunits: Methyltransferase-like protein 3 (METTL3), Methyltransferase-like protein 14 (METTL14) and Wilms tumor 1-associating protein (WTAP), and erased by two independent demethylases, Fat mass and obesity associated protein (FTO) and AlkB homolog 5 (ALKBH5). RNA demthylase ALKBH5 has been reported to play vital roles in several biological processes. However, very little is known about the role of ALKBH5 in cancer in general and breast tumorigenesis in particular. In this study, we report that ALKBH5 promotes breast cancer growth and progression. Using in vitro and in vivo models, we show that silencing of ALKBH5 inhibits breast cancer growth and invasion. Importantly, our studies reveal that ALKBH5 mediates its pro-tumorigenic function by regulating several microtubule associated genes including KIF2C, PLK1, MAPRE1 and RCC2 that are critical for spindle formation or assembly during mitotic progression. Interestingly, ALKBH5 target genes KIF2C and MAPRE1 are highly expressed in breast cancer patients and their higher expression is strongly correlated with lower survival of breast cancer patients. We believe that an optimal level of RNA methylation of key target genes is critical for normal cell cycle progression and any alteration in the levels of RNA methylation may alter activity or expression of these genes resulting in unabated cell proliferation. Citation Format: Vijay Kumar Eedunuri, Panneerdoss Subbarayalu, Subhapriya Rajamanickam, Abdelfattah Nourhan, Benjamin C. Onyeagucha, Santosh Timilsina, Pooja Yadav, Manjeet K. Rao. RNA demethylase alkbh5 supports breast cancer growth and progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3343. doi:10.1158/1538-7445.AM2017-3343
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have