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01-06-2016 | Original Article

miR-363 induces transdifferentiation of human kidney tubular cells to mesenchymal phenotype

Authors: Ryuji Morizane, Shizuka Fujii, Toshiaki Monkawa, Ken Hiratsuka, Shintaro Yamaguchi, Koichiro Homma, Hiroshi Itoh

Published in: Clinical and Experimental Nephrology | Issue 3/2016

Abstract

Background

microRNAs (miRNAs) are non-coding small RNAs that regulate embryonic development, cell differentiation and pathological processes via interaction with mRNA. Epithelial–mesenchymal transition (EMT) is pathological process that involves in a variety of diseases such as cancer or fibrosis.

Methods

In this study, we identified miR-363 as a potent inducer of EMT by microarray analysis in human kidney tubular cells, and analyzed the function and mechanisms of miR-363.

Results

Overexpression of miR-363 induced mesenchymal phenotypes with loss of epithelial phenotypes in human kidney tubular cells. In addition, in vitro scratch assay demonstrated that miR-363 promotes cell migration of primary culture of human kidney tubular cells. We identified TWIST/canonical WNT pathway as the downstream effecter of miR-363, and inhibition of canonical WNT by small molecule, IWR-1, attenuated EMT induced by miR-363.

Conclusion

miR-363 induces transdifferentiation of human kidney tubular cells via upregulation of TWIST/canonical WNT pathway.

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Rowe RG, Lin Y, Shimizu-Hirota R, Hanada S, Neilson EG, Greenson JK, et al. Hepatocyte-derived Snail1 propagates liver fibrosis progression. Mol Cell Biol. 2011;31(12):2392–403. doi:10.1128/MCB.01218-10.CrossRefPubMedPubMedCentral

Bates RC, Mercurio AM. The epithelial–mesenchymal transition (EMT) and colorectal cancer progression. Cancer Biol Ther. 2005;4(4):365–70.CrossRefPubMed

Kang Y, Massague J. Epithelial–mesenchymal transitions: twist in development and metastasis. Cell. 2004;118(3):277–9. doi:10.1016/j.cell.2004.07.011.CrossRefPubMed

Rastaldi MP, Ferrario F, Giardino L, Dell’Antonio G, Grillo C, Grillo P, et al. Epithelial–mesenchymal transition of tubular epithelial cells in human renal biopsies. Kidney Int. 2002;62(1):137–46. doi:10.1046/j.1523-1755.2002.00430.x.CrossRefPubMed

Das S, Becker BN, Hoffmann FM, Mertz JE. Complete reversal of epithelial to mesenchymal transition requires inhibition of both ZEB expression and the Rho pathway. BMC Cell Biol. 2009;10:94. doi:10.1186/1471-2121-10-94.CrossRefPubMedPubMedCentral

Yoshino J, Monkawa T, Tsuji M, Inukai M, Itoh H, Hayashi M. Snail1 is involved in the renal epithelial–mesenchymal transition. Biochem Biophys Res Commun. 2007;362(1):63–8. doi:10.1016/j.bbrc.2007.07.146.CrossRefPubMed

Lin CY, Tsai PH, Kandaswami CC, Lee PP, Huang CJ, Hwang JJ, et al. Matrix metalloproteinase-9 cooperates with transcription factor Snail to induce epithelial–mesenchymal transition. Cancer Sci. 2011;102(4):815–27. doi:10.1111/j.1349-7006.2011.01861.x.CrossRefPubMed

Okada H, Danoff TM, Kalluri R, Neilson EG. Early role of Fsp1 in epithelial–mesenchymal transformation. Am J Physiol. 1997;273(4 Pt 2):F563–74.PubMed

Li CW, Xia W, Huo L, Lim SO, Wu Y, Hsu JL, et al. Epithelial–mesenchyme transition induced by TNF-a requires NF-kB mediated transcriptional upregulation of Twist1. Cancer Res. 2012;. doi:10.1158/0008-5472.CAN-11-3123.

10.

Fang X, Cai Y, Liu J, Wang Z, Wu Q, Zhang Z, et al. Twist2 contributes to breast cancer progression by promoting an epithelial–mesenchymal transition and cancer stem-like cell self-renewal. Oncogene. 2011;30(47):4707–20. doi:10.1038/onc.2011.181.CrossRefPubMed

11.

Bhowmick NA, Ghiassi M, Bakin A, Aakre M, Lundquist CA, Engel ME, et al. Transforming growth factor-beta1 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism. Mol Biol Cell. 2001;12(1):27–36.CrossRefPubMedPubMedCentral

12.

Kalluri R, Weinberg RA. The basics of epithelial–mesenchymal transition. J Clin Investig. 2009;119(6):1420–8. doi:10.1172/JCI39104.CrossRefPubMedPubMedCentral

13.

Ambros V. The functions of animal microRNAs. Nature. 2004;431(7006):350–5. doi:10.1038/nature02871.CrossRefPubMed

14.

Bullock MD, Sayan AE, Packham GK, Mirnezami AH. MicroRNAs: critical regulators of epithelial to mesenchymal (EMT) and mesenchymal to epithelial transition (MET) in cancer progression. Biol Cell/Under Auspices Eur Cell Biol Organ. 2012;104(1):3–12. doi:10.1111/boc.201100115.CrossRef

15.

Wienholds E, Koudijs MJ, van Eeden FJ, Cuppen E, Plasterk RH. The microRNA-producing enzyme Dicer1 is essential for zebrafish development. Nat Genet. 2003;35(3):217–8. doi:10.1038/ng1251.CrossRefPubMed

16.

Ho J, Ng KH, Rosen S, Dostal A, Gregory RI, Kreidberg JA. Podocyte-specific loss of functional microRNAs leads to rapid glomerular and tubular injury. J Am Soc Nephrol: JASN. 2008;19(11):2069–75. doi:10.1681/ASN.2008020162.CrossRefPubMedPubMedCentral

17.

Wei Q, Bhatt K, He HZ, Mi QS, Haase VH, Dong Z. Targeted deletion of Dicer from proximal tubules protects against renal ischemia–reperfusion injury. J Am Soc Nephrol: JASN. 2010;21(5):756–61. doi:10.1681/ASN.2009070718.CrossRefPubMedPubMedCentral

18.

Racusen LC, Monteil C, Sgrignoli A, Lucskay M, Marouillat S, Rhim JG, et al. Cell lines with extended in vitro growth potential from human renal proximal tubule: characterization, response to inducers, and comparison with established cell lines. J Lab Clin Med. 1997;129(3):318–29.CrossRefPubMed

19.

Liang CC, Park AY, Guan JL. In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc. 2007;2(2):329–33. doi:10.1038/nprot.2007.30.CrossRefPubMed

20.

Zhao XL, Sun T, Che N, Sun D, Zhao N, Dong XY, et al. Promotion of hepatocellular carcinoma metastasis through matrix metalloproteinase activation by epithelial–mesenchymal transition regulator Twist1. J Cell Mol Med. 2011;15(3):691–700. doi:10.1111/j.1582-4934.2010.01052.x.CrossRefPubMedPubMedCentral

21.

Li J, Zhou BP. Activation of beta-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters. BMC Cancer. 2011;11:49. doi:10.1186/1471-2407-11-49.CrossRefPubMedPubMedCentral

22.

Chen B, Dodge ME, Tang W, Lu J, Ma Z, Fan CW, et al. Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Nat Chem Biol. 2009;5(2):100–7. doi:10.1038/nchembio.137.CrossRefPubMedPubMedCentral

23.

Wald AI, Hoskins EE, Wells SI, Ferris RL, Khan SA. Alteration of microRNA profiles in squamous cell carcinoma of the head and neck cell lines by human papillomavirus. Head Neck. 2011;33(4):504–12. doi:10.1002/hed.21475.CrossRefPubMedPubMedCentral

24.

Georgieva B, Milev I, Minkov I, Dimitrova I, Bradford AP, Baev V. Characterization of the uterine leiomyoma microRNAome by deep sequencing. Genomics. 2012;99(5):275–81. doi:10.1016/j.ygeno.2012.03.003.CrossRefPubMed

25.

Beltran AS, Russo A, Lara H, Fan C, Lizardi PM, Blancafort P. Suppression of breast tumor growth and metastasis by an engineered transcription factor. PLoS One. 2011;6(9):e24595. doi:10.1371/journal.pone.0024595.CrossRefPubMedPubMedCentral

26.

Eckert MA, Lwin TM, Chang AT, Kim J, Danis E, Ohno-Machado L, et al. Twist1-induced invadopodia formation promotes tumor metastasis. Cancer Cell. 2011;19(3):372–86. doi:10.1016/j.ccr.2011.01.036.CrossRefPubMedPubMedCentral

27.

Peinado H, Olmeda D, Cano A. Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer. 2007;7(6):415–28. doi:10.1038/nrc2131.CrossRefPubMed

28.

Tan EJ, Thuault S, Caja L, Carletti T, Heldin CH, Moustakas A. Regulation of transcription factor Twist expression by the DNA architectural protein high mobility group A2 during epithelial-to-mesenchymal transition. J Biol Chem. 2012;287(10):7134–45. doi:10.1074/jbc.M111.291385.CrossRefPubMedPubMedCentral

29.

Sun S, Du R, Xia L, Sun W, Zhai Y, Yu Y, et al. Twist is a new prognostic marker for renal survival in patients with chronic kidney disease. Am J Nephrol. 2012;35(2):141–51. doi:10.1159/000335191.CrossRefPubMed

30.

Khan MA, Chen HC, Zhang D, Fu J. Twist: a molecular target in cancer therapeutics. Tumour Biol: J Int Soc Oncodev Biol Med. 2013;34(5):2497–506. doi:10.1007/s13277-013-1002-x.CrossRef

Title: miR-363 induces transdifferentiation of human kidney tubular cells to mesenchymal phenotype
Authors: Ryuji Morizane
Shizuka Fujii
Toshiaki Monkawa
Ken Hiratsuka
Shintaro Yamaguchi
Koichiro Homma
Hiroshi Itoh
Publication date: 01-06-2016
Publisher: Springer Japan
Published in: Clinical and Experimental Nephrology / Issue 3/2016
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI: https://doi.org/10.1007/s10157-015-1167-2

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Abstract

Background

Methods

Results

Conclusion

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