LAUSR

Increasing research interests have been aroused in exploring the function of long non-coding RNA (lncRNA) in breast cancer and developing lncRNA-targeted diagnosis, treatment and prognosis. In GEPIA2 database, we compared the expression pattern of the lncRNA RP11-214F16.8 in normal mammary tissues and breast cancer tumors and its correlation with the overall death rate of breast cancer patients. Gain- and loss-of function assays were employed to study function of the lncRNA in breast cancer cell lines in vitro while xenograft tumor growth assay was performed to investigate its function in tumorigenesis in vivo. We also used RNA pull-down coupled with mass spectrometry to identify the lncRNA binding partner, and RIP, EMSA, ChIP and Co-IP assays as well to testify these physical interactions.We identified that up-regulation of the lncRNA RP11-214F16.8 is subtype-independently associated with a higher overall death rate in breast cancer patients. Increased RP11-214F16.8 expression endows breast cancer cells enhanced capabilities in the aspects of proliferation, invasion, migration and tumor-initiation, while loss of the lncRNA exerts the opposite effects. Mechanistically, the oncogenic property of RP11-214F16.8 lies to its post-translational repression on the tumor suppressor NISCH via recruiting SENP3-mediated de-SUMOylation and ubiquitin-proteasome-mediated protein degradation. NISCH in turn inhibits the transcription of RP11-214F16.8 through restraining the expression of the transcription factors located downstream of RAC1, PAK1 and ERK1/2 signaling transduction pathways. In all, dysregulation of RP11-214F16.8 not only stimulates activation of the proliferation- and migration-promoting signaling cascades, but also facilitates the removal of restrictions on self-transcription, which ensures the progression of tumorigenesis.