The lncRNA BORG Drives Breast Cancer Metastasis and Disease Recurrence

Long noncoding RNAs (lncRNAs) have emerged as potent regulators of breast cancer development and progression, including the metastatic spread of disease. Through in silico and biological analyses, investigators at Case Western Reserve University identified a novel lncRNA, BMP/OP-Responsive Gene (BORG), whose expression directly correlates with aggressive breast cancer phenotypes, as well as with metastatic competence and disease recurrence in multiple clinical cohorts. Mechanistically, BORG elicits the metastatic outgrowth of latent breast cancer cells by promoting the localization and transcriptional repressive activity of TRIM28, which binds BORG and induces substantial alterations in carcinoma proliferation and survival. Moreover, inhibiting BORG expression in metastatic breast cancer cells impedes their metastatic colonization of the lungs of mice, implying that BORG acts as a novel driver of the genetic and epigenetic alterations that underlie the acquisition of metastatic and recurrent phenotypes by breast cancer cells.

BORG confers a unique genome-wide transcriptional signature to latent D2.OR cells


(ac) Volcano plots showing differentially expressed transcripts in D2.OR-BORG versus parental D2.OR cells (a), D2.OR-BORG versus TRIM28-deficient D2.OR-BORG cells (b), and parental D2.OR versus TRIM28-deficient D2.OR-BORG cells (c) grown in 3D-culture for 7 days prior to Affymetrix GeneChip Mouse Gene 2.0 ST Array analysis. Cut-off criteria was an absolute change ≥ 2.0-fold (*P < 0.05). (d) Hierarchical clustering of transcriptional signatures arising from ~1150 genes whose expression was significantly altered in the three groups analyzed in Panels A–C. Fold difference in expression of p21 and gadd45a in D2.OR-BORG cells versus parental D2.OR cells is annotated. (e) Hierarchical heatmap obtained using the Downstream Effects Analysis feature of IPA software to define BORG-regulated biological processes. Representative biological functions expanded in subpanels. Z-score represents a statistical measure of the activation state of each biological process (increased: orange; decreased: blue). (f) GSEA demonstrated enrichment of the hallmark KRAS gene signature in D2.OR-BORG cells versus their parental counterparts.

Gooding AJ, Zhang B, Jahanbani FK, Gilmore HL, Chang JC, Valadkhan S, Schiemann WP. (2017) The lncRNA BORG Drives Breast Cancer Metastasis and Disease Recurrence. Sci Rep 7(1):12698. [article]

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