Long non-coding RNA UASR1 promotes proliferation and migration of breast cancer cells through the AKT/mTOR pathway

: Long non-coding RNAs (lncRNAs) are non-coding RNAs longer than 200 nucleotides that function as regulatory factors in many human diseases, including cancer. However, majority of lncRNAs remain to be characterized. In this study, we characterized a novel lncRNA transcript, named UNC5B antisense RNA1 (UASR1). UASR1 is 647bp in length consisting of two exons. This lncRNA is an antisense of intron 1 of unc-5 netrin receptor B (UNC5B) gene. In breast cancer tissues, UASR1 was upregulated. Ectopic expression of UASR1 promoted proliferation and clonogenic growth of breast cancer cells MCF7 and MDA-MB-231. The migration of these cells also increased as demonstrated by wound healing and transwell assays. In contrast, silencing of UASR1 suppressed cell proliferation and migration. Further studies showed that UASR1 activated AKT and AKT-mediated mTOR signaling pathway to stimulate cell proliferation and growth. In these cells, active pAKT, pTSC2, p4EBP1 and pp70S6K were increased. Taken together, our data suggest that UASR1 plays an oncogenic role in breast cancer cells through activation of the AKT/mTOR signaling pathway, being a novel RNA oncogene.