LncRNA ANCR Down-regulation Promotes TGF-β-induced EMT and Metastasis in Breast Cancer

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 Oct 6

PMID 28978036

Citations 51

Authors

Zhongwei Li

Meichen Dong

Dongmei Fan

Pingfu Hou

Hongyuan Li

Lingxia Liu

Cong Lin

Jiwei Liu

Liangping Su

Lan Wu

Xiaoxue Li

Baiqu Huang

Jun Lu

Yu Zhang

Affiliations

Soon will be listed here.

Abstract

Epithelial to mesenchymal transition (EMT) is a progression of cellular plasticity critical for development, differentiation, cancer cells migration and tumor metastasis. As a well-studied factor, TGF-β participates in EMT and involves in physiological and pathological functions of tumor progression. Accumulating evidence indicates that long noncoding RNAs(lncRNAs) play crucial roles in EMT and tumor metastasis. Here, we find that lncRNA ANCR participates in TGF-β1-induced EMT. By our ChIP and Real-time PCR assays, we reveal that TGF-β1 down-regulates ANCR expression by increasing HDAC3 enrichment at ANCR promoter region, which decreases both H3 and H4 acetylation of ANCR promoter. In addition, by western blot and transwell assays, we indicate that ectopic expression of ANCR partly attenuates the TGF-β1-induced EMT. Downstream, ANCR inhibits breast cancer cell migration and breast cancer metastasis by decreasing RUNX2 expression and . Thus, our study identifies ANCR, as a new TGF-β downstream molecular, is essential for TGF-β1-induced EMT by decreasing RUNX2 expression. These results implicate that ANCR might become a prognostic biomarker and an anti-metastasis therapy target for breast cancer.

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References

Lee K, Hong S, Bae S . Both the Smad and p38 MAPK pathways play a crucial role in Runx2 expression following induction by transforming growth factor-beta and bone morphogenetic protein. Oncogene. 2002; 21(47):7156-63. DOI: 10.1038/sj.onc.1205937. View

van der Deen M, Akech J, Lapointe D, Gupta S, Young D, Montecino M . Genomic promoter occupancy of runt-related transcription factor RUNX2 in Osteosarcoma cells identifies genes involved in cell adhesion and motility. J Biol Chem. 2011; 287(7):4503-17. PMC: 3281617. DOI: 10.1074/jbc.M111.287771. View

Zavadil J, Bottinger E . TGF-beta and epithelial-to-mesenchymal transitions. Oncogene. 2005; 24(37):5764-74. DOI: 10.1038/sj.onc.1208927. View

Yuan J, Yang F, Wang F, Ma J, Guo Y, Tao Q . A long noncoding RNA activated by TGF-β promotes the invasion-metastasis cascade in hepatocellular carcinoma. Cancer Cell. 2014; 25(5):666-81. DOI: 10.1016/j.ccr.2014.03.010. View

Chen X, Xiao W, Chen W, Luo L, Ye S, Liu Y . The epigenetic modifier trichostatin A, a histone deacetylase inhibitor, suppresses proliferation and epithelial-mesenchymal transition of lens epithelial cells. Cell Death Dis. 2013; 4:e884. PMC: 3920942. DOI: 10.1038/cddis.2013.416. View

Bae G, Hong S, Park J, Kwon O, Kim K, Koo J . Chronic TGFβ stimulation promotes the metastatic potential of lung cancer cells by Snail protein stabilization through integrin β3-Akt-GSK3β signaling. Oncotarget. 2016; 7(18):25366-76. PMC: 5041910. DOI: 10.18632/oncotarget.8295. View

Zhu L, Xu P . Downregulated LncRNA-ANCR promotes osteoblast differentiation by targeting EZH2 and regulating Runx2 expression. Biochem Biophys Res Commun. 2013; 432(4):612-7. DOI: 10.1016/j.bbrc.2013.02.036. View

Bray F, McCarron P, Parkin D . The changing global patterns of female breast cancer incidence and mortality. Breast Cancer Res. 2004; 6(6):229-39. PMC: 1064079. DOI: 10.1186/bcr932. View

Thiery J, Acloque H, Huang R, Nieto M . Epithelial-mesenchymal transitions in development and disease. Cell. 2009; 139(5):871-90. DOI: 10.1016/j.cell.2009.11.007. View

10.

Kalluri R, Weinberg R . The basics of epithelial-mesenchymal transition. J Clin Invest. 2009; 119(6):1420-8. PMC: 2689101. DOI: 10.1172/JCI39104. View

11.

Schmitt A, Chang H . Long Noncoding RNAs in Cancer Pathways. Cancer Cell. 2016; 29(4):452-463. PMC: 4831138. DOI: 10.1016/j.ccell.2016.03.010. View

12.

Wysokinski D, Blasiak J, Pawlowska E . Role of RUNX2 in Breast Carcinogenesis. Int J Mol Sci. 2015; 16(9):20969-93. PMC: 4613236. DOI: 10.3390/ijms160920969. View

13.

Owens T, Rogers R, Best S, Ledger A, Mooney A, Ferguson A . Runx2 is a novel regulator of mammary epithelial cell fate in development and breast cancer. Cancer Res. 2014; 74(18):5277-5286. PMC: 4178131. DOI: 10.1158/0008-5472.CAN-14-0053. View

14.

Chimge N, Baniwal S, Little G, Chen Y, Kahn M, Tripathy D . Regulation of breast cancer metastasis by Runx2 and estrogen signaling: the role of SNAI2. Breast Cancer Res. 2011; 13(6):R127. PMC: 3326569. DOI: 10.1186/bcr3073. View

15.

Yang S, Yao H, Li M, Li H, Wang F . Long Non-Coding RNA MALAT1 Mediates Transforming Growth Factor Beta1-Induced Epithelial-Mesenchymal Transition of Retinal Pigment Epithelial Cells. PLoS One. 2016; 11(3):e0152687. PMC: 4809592. DOI: 10.1371/journal.pone.0152687. View

16.

Piek E, Moustakas A, Kurisaki A, Heldin C, Ten Dijke P . TGF-(beta) type I receptor/ALK-5 and Smad proteins mediate epithelial to mesenchymal transdifferentiation in NMuMG breast epithelial cells. J Cell Sci. 1999; 112 ( Pt 24):4557-68. DOI: 10.1242/jcs.112.24.4557. View

17.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

18.

Tan C, Li G, Tan L, Du X, Li X, He R . Breast cancer cells obtain an osteomimetic feature via epithelial-mesenchymal transition that have undergone BMP2/RUNX2 signaling pathway induction. Oncotarget. 2016; 7(48):79688-79705. PMC: 5346745. DOI: 10.18632/oncotarget.12939. View

19.

Lamouille S, Xu J, Derynck R . Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 2014; 15(3):178-96. PMC: 4240281. DOI: 10.1038/nrm3758. View

20.

Farina N, Zingiryan A, Akech J, Callahan C, Lu H, Stein J . A microRNA/Runx1/Runx2 network regulates prostate tumor progression from onset to adenocarcinoma in TRAMP mice. Oncotarget. 2016; 7(43):70462-70474. PMC: 5342565. DOI: 10.18632/oncotarget.11992. View