The tenacity of late recurrence of estrogen receptor (ER)-positive breast cancer remains a major clinical issue to overcome. The administration of endocrine therapies within the first 5 years substantially minimizes the risk of relapse; however, some tumors reappear 10-20 years after the initial diagnosis. Accumulating evidence has strengthened the notion that long non-coding RNAs (lncRNAs) are associated with cancer in various respects. Because lncRNAs may display high tissue/cell-specificity, we hypothesized this might provide new insights to tumor recurrence. By comparing transcriptome profiles of 24 clinical primary tumors obtained from patients who developed distant metastases and patients with no signs of recurrence, we identified lncRNA NR2F1-AS1 whose expression was associated with tumor recurrence. We revealed the relationship between NR2F1-AS1 and the hormone receptor expressions in ER-positive breast cancer cells. Gain-of-function of NR2F1-AS1 steered cancer cells into quiescence-like state by the upregulation of dormancy inducers and pluripotency markers, and activates representative events of the metastatic cascade. Our findings implicated NR2F1-AS1 in the dynamics of tumor recurrence in ER-positive breast cancers, and introduce a new biomarker that holds a therapeutic potential, providing favorable prospects to be translated into the clinical field.
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