LincRNA-RoR and MiR-145 Regulate Invasion in Triple-negative Breast Cancer Via Targeting ARF6

Overview

Journal Mol Cancer Res

Specialty Cell Biology

Date 2014 Sep 26

PMID 25253741

Citations 123

Authors

Gabriel Eades

Benjamin Wolfson

Yongshu Zhang

Qinglin Li

Yuan Yao

Qun Zhou

Affiliations

Soon will be listed here.

Abstract

Unlabelled: 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.

Implications: The lincRNA-RoR/miR-145/ARF6 pathway is critical to TNBC metastasis and could serve as biomarkers or therapeutic targets for improving survival.

Citing Articles

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Deciphering the code: the pivotal role of lncRNAs in advancing TNBC therapy.

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References

Grossmann A, Yoo J, Clancy J, Sorensen L, Sedgwick A, Tong Z . The small GTPase ARF6 stimulates β-catenin transcriptional activity during WNT5A-mediated melanoma invasion and metastasis. Sci Signal. 2013; 6(265):ra14. PMC: 3961043. DOI: 10.1126/scisignal.2003398. View

Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O, Chinappi M . A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell. 2011; 147(2):358-69. PMC: 3234495. DOI: 10.1016/j.cell.2011.09.028. View

Muralidharan-Chari V, Hoover H, Clancy J, Schweitzer J, Suckow M, Schroeder V . ADP-ribosylation factor 6 regulates tumorigenic and invasive properties in vivo. Cancer Res. 2009; 69(6):2201-9. PMC: 3761373. DOI: 10.1158/0008-5472.CAN-08-1301. View

Hashimoto S, Onodera Y, Hashimoto A, Tanaka M, Hamaguchi M, Yamada A . Requirement for Arf6 in breast cancer invasive activities. Proc Natl Acad Sci U S A. 2004; 101(17):6647-52. PMC: 404099. DOI: 10.1073/pnas.0401753101. View

Li J, Liu S, Zhou H, Qu L, Yang J . starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 2013; 42(Database issue):D92-7. PMC: 3964941. DOI: 10.1093/nar/gkt1248. View

Hu B, Shi B, Jarzynka M, Yiin J, DSouza-Schorey C, Cheng S . ADP-ribosylation factor 6 regulates glioma cell invasion through the IQ-domain GTPase-activating protein 1-Rac1-mediated pathway. Cancer Res. 2009; 69(3):794-801. PMC: 2633432. DOI: 10.1158/0008-5472.CAN-08-2110. View

Foulkes W, Smith I, Reis-Filho J . Triple-negative breast cancer. N Engl J Med. 2010; 363(20):1938-48. DOI: 10.1056/NEJMra1001389. View

Harrow J, Frankish A, Gonzalez J, Tapanari E, Diekhans M, Kokocinski F . GENCODE: the reference human genome annotation for The ENCODE Project. Genome Res. 2012; 22(9):1760-74. PMC: 3431492. DOI: 10.1101/gr.135350.111. View

Valderrama F, Ridley A . Getting invasive with GEP100 and Arf6. Nat Cell Biol. 2008; 10(1):16-8. DOI: 10.1038/ncb0108-16. View

10.

Wang Y, Xu Z, Jiang J, Xu C, Kang J, Xiao L . Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal. Dev Cell. 2013; 25(1):69-80. DOI: 10.1016/j.devcel.2013.03.002. View

11.

Chiyomaru T, Enokida H, Tatarano S, Kawahara K, Uchida Y, Nishiyama K . miR-145 and miR-133a function as tumour suppressors and directly regulate FSCN1 expression in bladder cancer. Br J Cancer. 2010; 102(5):883-91. PMC: 2833258. DOI: 10.1038/sj.bjc.6605570. View

12.

Eades G, Yang M, Yao Y, Zhang Y, Zhou Q . miR-200a regulates Nrf2 activation by targeting Keap1 mRNA in breast cancer cells. J Biol Chem. 2011; 286(47):40725-33. PMC: 3220489. DOI: 10.1074/jbc.M111.275495. View

13.

Guttman M, Amit I, Garber M, French C, Lin M, Feldser D . Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 2009; 458(7235):223-7. PMC: 2754849. DOI: 10.1038/nature07672. View

14.

Morishige M, Hashimoto S, Ogawa E, Toda Y, Kotani H, Hirose M . GEP100 links epidermal growth factor receptor signalling to Arf6 activation to induce breast cancer invasion. Nat Cell Biol. 2007; 10(1):85-92. DOI: 10.1038/ncb1672. View

15.

Carey L, Perou C, Livasy C, Dressler L, Cowan D, Conway K . Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. 2006; 295(21):2492-502. DOI: 10.1001/jama.295.21.2492. View

16.

Tay Y, Kats L, Salmena L, Weiss D, Tan S, Ala U . Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs. Cell. 2011; 147(2):344-57. PMC: 3235920. DOI: 10.1016/j.cell.2011.09.029. View

17.

Siegel R, Ward E, Brawley O, Jemal A . Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011; 61(4):212-36. DOI: 10.3322/caac.20121. View

18.

Iorio M, Ferracin M, Liu C, Veronese A, Spizzo R, Sabbioni S . MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005; 65(16):7065-70. DOI: 10.1158/0008-5472.CAN-05-1783. View

19.

Li Q, Yao Y, Eades G, Liu Z, Zhang Y, Zhou Q . Downregulation of miR-140 promotes cancer stem cell formation in basal-like early stage breast cancer. Oncogene. 2013; 33(20):2589-600. PMC: 3883868. DOI: 10.1038/onc.2013.226. View

20.

Friedman R, Farh K, Burge C, Bartel D . Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2008; 19(1):92-105. PMC: 2612969. DOI: 10.1101/gr.082701.108. View