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 - Funding Information:
Members of the Schiemann Laboratory are thanked for critical comments and reading of the manuscript. We also thank Dr. Lalith Gunawardane for technical assistance in elucidating BORG-bindings partners, as well as acknowledge the expertise provided by members of the Case Comprehensive Cancer Center’s Core Facilities, including the Gene Expression & Genotyping Core, the Imaging Research Core, and Tissue Resources Core. Research support was provided in part by the National Institutes of Health to W.P.S. (CA129359, CA177069, and CA194518) and A.J.G (T32GM007250 and F30CA203233). Additional support was graciously provided by the METAvivor Foundation (W.P.S), and by pilot funding from the Case Comprehensive Cancer Center’s Research Innovation Fund, which is supported by the Case Council and Friends of the Case Comprehensive Cancer Center (W.P.S. and S.V.).
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
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 12698
ER -