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Unlabelled: Twist-1 and miRNAs have been reported to be associated with tumor metastasis and angiogenesis. However, the relationship between Twist-1 and miRNAs and the function of miRNAs remain largely undefined. We aimed to reveal the Twist-1-related miRNA expression profile and to determine whether Twist-1 functions in tumor metastasis and vasculogenic mimicry (VM) by regulating miRNA expression in hepatocellular carcinoma (HCC). Results showed that the expression of miR-27a-3p was consistently down-regulated in HCC cell lines and tissue samples displaying high expression of Twist-1. Both loss- and gain-of-function assays revealed suppressive effects of miR-27a-3p. Low miR-27a-3p expression was significantly associated with early metastasis in HCC. Subsequent investigations revealed that miR-27a-3p mediated the inhibition of epithelial-mesenchymal transition (EMT). Additional experiments showed that VE-cadherin is a direct target of miR-27a-3p and further demonstrated the critical role of miR-27a-3p in suppressing tumor metastasis and VM.

Conclusions: Twist-1 up-regulation in HepG2 cells resulted in the differential expression of 18 miRNAs. Among them, miR-27a-3p deregulation contributed to VM and metastasis. The miR-27a-3p-mediated down-regulation of VE-cadherin and inhibition of EMT may be essential for Twist-1 to induce tumor metastasis and VM. Our findings highlight the importance of miR-27a-3p and suggest a promising new strategy for anti-HCC therapy.

Titel:	miR-27a-3p suppresses tumor metastasis and VM by down-regulating VE-cadherin expression and inhibiting EMT: an essential role for Twist-1 in HCC.
Autor/in / Beteiligte Person:	Zhao, N ; Sun, H ; Sun, B ; Zhu, D ; Zhao, X ; Wang, Y ; Gu, Q ; Dong, X ; Liu, F ; Zhang, Y ; Li, X
Zeitschrift:	Scientific reports, Jg. 6 (2016-03-16), S. 23091
Veröffentlichung:	London : Nature Publishing Group, copyright 2011-, 2016
Medientyp:	academicJournal
ISSN:	2045-2322 (electronic)
DOI:	10.1038/srep23091
Schlagwort:	3' Untranslated Regions genetics Animals Antigens, CD metabolism Biological Mimicry genetics Blotting, Western Cadherins metabolism Carcinoma, Hepatocellular metabolism Carcinoma, Hepatocellular pathology Cell Line, Tumor Down-Regulation Female Gene Expression Profiling methods Gene Expression Regulation, Neoplastic HEK293 Cells Hep G2 Cells Humans Liver Neoplasms metabolism Liver Neoplasms pathology Mice, Inbred BALB C Mice, Nude Microscopy, Fluorescence Neoplasm Metastasis Neovascularization, Pathologic genetics Nuclear Proteins metabolism Reverse Transcriptase Polymerase Chain Reaction Transplantation, Heterologous Twist-Related Protein 1 metabolism Antigens, CD genetics Cadherins genetics Carcinoma, Hepatocellular genetics Epithelial-Mesenchymal Transition genetics Liver Neoplasms genetics MicroRNAs genetics Nuclear Proteins genetics Twist-Related Protein 1 genetics
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Sci Rep] 2016 Mar 16; Vol. 6, pp. 23091. <i>Date of Electronic Publication: </i>2016 Mar 16. MeSH Terms: Antigens, CD / genetics ; Cadherins / genetics ; Carcinoma, Hepatocellular / genetics ; Epithelial-Mesenchymal Transition / genetics ; Liver Neoplasms / genetics ; MicroRNAs / genetics ; Nuclear Proteins / genetics ; Twist-Related Protein 1 / genetics ; 3' Untranslated Regions / genetics ; Animals ; Antigens, CD / metabolism ; Biological Mimicry / genetics ; Blotting, Western ; Cadherins / metabolism ; Carcinoma, Hepatocellular / metabolism ; Carcinoma, Hepatocellular / pathology ; Cell Line, Tumor ; Down-Regulation ; Female ; Gene Expression Profiling / methods ; Gene Expression Regulation, Neoplastic ; HEK293 Cells ; Hep G2 Cells ; Humans ; Liver Neoplasms / metabolism ; Liver Neoplasms / pathology ; Mice, Inbred BALB C ; Mice, Nude ; Microscopy, Fluorescence ; Neoplasm Metastasis ; Neovascularization, Pathologic / genetics ; Nuclear Proteins / metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transplantation, Heterologous ; Twist-Related Protein 1 / metabolism References: PLoS One. 2012;7(12):e51702. (PMID: 23240057) ; Oncogene. 2015 Sep 17;34(38):4952-63. (PMID: 25597410) ; PLoS One. 2014;9(8):e105991. (PMID: 25166914) ; Oncotarget. 2015 Aug 28;6(25):21645-54. (PMID: 26046464) ; Tumour Biol. 2014 Aug;35(8):7335-42. (PMID: 24880591) ; J Biol Chem. 2010 Jan 1;285(1):226-33. (PMID: 19897486) ; Mol Cancer Ther. 2014 Dec;13(12):3107-22. (PMID: 25277383) ; Methods. 2001 Dec;25(4):402-8. (PMID: 11846609) ; Nat Protoc. 2008;3(4):698-709. (PMID: 18388953) ; Histol Histopathol. 2015 Nov;30(11):1283-94. (PMID: 26084282) ; Int J Oncol. 2013 Feb;42(2):391-402. (PMID: 23229173) ; J Clin Oncol. 2011 Dec 20;29(36):4781-8. (PMID: 22105822) ; Oncogene. 2014 Feb 6;33(6):679-89. (PMID: 23353819) ; Adv Drug Deliv Rev. 2015 Jan;81:128-41. (PMID: 24859533) ; Pharmacol Ther. 2015 Jun;150:33-46. (PMID: 25595324) ; Haematologica. 2013 Mar;98(3):414-9. (PMID: 22983574) ; Am J Pathol. 1999 Sep;155(3):739-52. (PMID: 10487832) ; Nucleic Acids Res. 2009 Jan;37(1):123-8. (PMID: 19029138) ; Int J Mol Sci. 2015;16(5):10921-33. (PMID: 26006230) ; Hepatol Res. 2009 Aug;39(8):786-94. (PMID: 19473441) ; Oncol Rep. 2014 Jan;31(1):280-6. (PMID: 24154848) ; Adv Drug Deliv Rev. 2015 Jan;81:62-74. (PMID: 25450260) ; BMC Cancer. 2014;14:678. (PMID: 25239093) ; Proc Natl Acad Sci U S A. 2013 May 21;110(21):8573-8. (PMID: 23650389) ; Oncogene. 2013 Oct 10;32(41):4873-82. (PMID: 23160379) ; Int J Oncol. 2015 Apr;46(4):1601-8. (PMID: 25626081) ; Cancer Biol Ther. 2006 Feb;5(2):228-33. (PMID: 16481735) ; Cell Death Dis. 2013;4:e574. (PMID: 23559009) ; Cell Tissue Res. 2014 Mar;355(3):523-7. (PMID: 24619142) ; Molecules. 2014;19(5):6393-406. (PMID: 24853455) ; Biochem Biophys Res Commun. 2011 May 20;408(4):686-91. (PMID: 21539816) ; World J Gastroenterol. 2014 Dec 21;20(47):17894-904. (PMID: 25548487) ; Int J Oncol. 2013 Feb;42(2):757-66. (PMID: 23254855) ; J Biomed Biotechnol. 2010;2010:956897. (PMID: 20490282) ; Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):8018-23. (PMID: 11416160) ; Oncotarget. 2015 Oct 13;6(31):30818-30. (PMID: 26360780) ; Cancer Lett. 2010 Dec 8;298(2):150-8. (PMID: 20638779) ; Hepatology. 2010 Feb;51(2):545-56. (PMID: 19957372) ; Oncogene. 2013 Oct 10;32(41):4871-2. (PMID: 23318416) Substance Nomenclature: 0 (3' Untranslated Regions) ; 0 (Antigens, CD) ; 0 (Cadherins) ; 0 (MIRN27 microRNA, human) ; 0 (MicroRNAs) ; 0 (Nuclear Proteins) ; 0 (TWIST1 protein, human) ; 0 (Twist-Related Protein 1) ; 0 (cadherin 5) Entry Date(s): Date Created: 20160317 Date Completed: 20170118 Latest Revision: 20220330 Update Code: 20231215 PubMed Central ID: PMC4793289

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miR-27a-3p suppresses tumor metastasis and VM by down-regulating VE-cadherin expression and inhibiting EMT: an essential role for Twist-1 in HCC.