TY - JOUR
T1 - The lncRNA BORG Drives Breast Cancer Metastasis and Disease Recurrence
AU - Gooding, Alex J.
AU - Zhang, Bing
AU - Jahanbani, Fereshteh Kenari
AU - Gilmore, Hannah L.
AU - Chang, Jenny C.
AU - Valadkhan, Saba
AU - Schiemann, William P.
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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, we 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.
AB - 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, we 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.
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U2 - 10.1038/s41598-017-12716-6
DO - 10.1038/s41598-017-12716-6
M3 - Article
C2 - 28983112
AN - SCOPUS:85030721338
SN - 2045-2322
VL - 7
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 12698
ER -