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 noncoding 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.