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Late-stage relapse (LSR) in patients with breast cancer (BC) occurs more than five years and up to 10 years after initial treatment and has less than 30% 5-year relative survival rate. Long non-coding RNAs (lncRNAs) play important roles in BC yet have not been studied in LSR BC. Here, we identify 1127 lncRNAs differentially expressed in LSR BC via transcriptome sequencing and analysis of 72 early-stage and 24 LSR BC patient tumors. Decreasing expression of the most up-regulated lncRNA,  LINC00355 , in BC and MCF7 long-term estrogen deprived cell lines decreases cellular invasion and proliferation. Subsequent mechanistic studies show that  LINC00355  binds to MENIN and changes occupancy at the  CDKN1B  promoter to decrease p27 Kip . In summary, this is a key study discovering lncRNAs in LSR BC and  LINC00355  association with epigenetic regulation and proliferation in BC.

LINC00355 regulates p27KIP expression by binding to MENIN to induce proliferation in late-stage relapse breast cancer