title: lincRNA-RoR and miR-145 regulate invasion in triple-negative breast cancer via targeting ARF6.
abstract: Triple-negative (ER(-), HER2(-), PR(-)) breast cancer (TNBC) is an aggressive disease with a poor prognosis with no available molecularly targeted therapy. Silencing of microRNA-145 (miR-145) may be a defining marker of TNBC based on molecular profiling and deep sequencing. Therefore, the molecular mechanism behind miR-145 downregulation in TNBC was examined. Overexpression of the long intergenic noncoding RNA regulator of reprogramming, lincRNA-RoR, functions as a competitive endogenous RNA sponge in TNBC. Interestingly, lincRNA-RoR is dramatically upregulated in TNBC and in metastatic disease and knockdown restores miR-145 expression. Previous reports suggest that miR-145 has growth-suppressive activity in some breast cancers; however, these data in TNBC indicate that miR-145 does not affect proliferation or apoptosis but instead, miR-145 regulates tumor cell invasion. Investigation of miR-145-regulated pathways involved in tumor invasion revealed a novel target, the small GTPase ADP-ribosylation factor 6 (Arf6). Subsequent analysis demonstrated that ARF6, a known regulator of breast tumor cell invasion, is dramatically upregulated in TNBC and in breast tumor metastasis. Mechanistically, ARF6 regulates E-cadherin localization and affects cell-cell adhesion. These results reveal a lincRNA-RoR/miR-145/ARF6 pathway that regulates invasion in TNBCs.
  
  
  CONCLUSIONS
  The lincRNA-RoR/miR-145/ARF6 pathway is critical to TNBC metastasis and could serve as biomarkers or therapeutic targets for improving survival.
authors.affiliation: Greenebaum Cancer Center, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Eades
authors.affiliation: Greenebaum Cancer Center, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wolfson
authors.affiliation: Greenebaum Cancer Center, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Yongshu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Greenebaum Cancer Center, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Greenebaum Cancer Center, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Greenebaum Cancer Center, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland. qzhou@som.umaryland.edu.
authors.forename: Qun
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
chemical_list: D000089982:ADP-Ribosylation Factor 6; C000588825:Linc-RNA-RoR, human; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human