MiR-200c suppresses the migration of retinoblastoma cells by reversing epithelial mesenchymal transition
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Corresponding Author:

Ling Gao. Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China. gaoling6287@163.com

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Supported by the National Natural Science Foundation of China (No.81072221); National Science Foundation of Hunan Province (No.14JJ2005).

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    Abstract:

    AIM: To analyze the relationship between clinical features and epithelial mesenchymal transition (EMT) in retinoblastoma (RB), further to investigate whether miR-200c regulates the EMT and migration of RB cells. METHODS: Expression of EMT-related markers and tumor-related factors were detected by immuno-histochemistry analysis in RB tissue from 29 cases. Correlations between their expression and clinical characteristics were analyzed. The regulation effects of miR-200c on EMT-related markers, tumor-related factors were observed in mRNA level and protein level by real-time polymerase chain reaction (PCR) and Western blot, respectively, in Y79 and Weri-rb1 cells. Its effects on migration force of these RB cell lines were also detected with Transwell test. RESULTS: Lower expression of E-cadherin was present in the cases with malignant prognosis. MiR-200c promoted the expression of E-cadherin and decreased the expression of Vimentin and N-cadherin in Y79 and Weri-rb1 cells. Migration force of RB cells could be inhibited by miR-200c. CONCLUSION: EMT might be associated with bad prognosis in RB. MiR-200c suppresses the migration of retinoblastomatous cells by reverse EMT.

    Reference
    1 Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol 2014;15(3):178-196.
    2 Mallini P, Lennard T, Kirby J, Meeson A. Epithelial-to-mesenchymal transition: what is the impact on breast cancer stem cells and drug resistance. Cancer Treat Rev 2014;40(3):341-348.
    3 Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 2009;9:265-273.
    4 Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell 2009;139(5):871-890.
    5 Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008;133(4):704-715.
    6 Sreenivasan S, Thirumalai K, Danda R, Krishnakumar S. Effect of curcumin on miRNA expression in human Y79 retinoblastoma cells. Curr Eye Res 2012;37(5):421-428.
    7 Park SM, Gaur AB, Lengyel E, Peter ME. The miR-200 family determines the epithelial phenotypeof cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev 2008;22:894-907.
    8 Jiang C, Chen X, Alattar M, Wei J, Liu H. MicroRNAs in tumorigenesis, metastasis, diagnosis and prognosis of gastric cancer. Cancer Gene Ther 2015;22(6):291-301.
    9 Pan Y, Meng M, Zhang G, Han H, Zhou Q. Oncogenic microRNAs in the genesis of leukemia and lymphoma. Curr Pharm Des 2014;20(33): 5260-5267.
    10 Lee M, Kim EJ, Jeon MJ. MicroRNAs 125a and 125b inhibit ovarian cancer cells through post-transcriptional inactivation of EIF4EBP1. Oncotarget 2016;7(8):8726-8742.
    11 Zhou CX, Wang CL, Yu AL, Wang QY, Zhan MN, Tang J, Gong XF, Yin QQ, He M, He JR, Chen GQ, Zhao Q. MiR-630 suppresses breast cancer progression by targeting metadherin. Oncotarget 2016;7(2): 1288-1299.
    12 Chen CP, Sun ZL, Lu X, Wu WX, Guo WL, Lu JJ, Han C, Huang JQ, Fang Y. miR-340 suppresses cell migration and invasion by targeting MYO10 in breast cancer. Oncol Rep 2016;35(2):709-716.
    13 Tryndyak VP, Beland FA, Pogribny IP. E-cadherin transcriptional down-regulation by epigenetic and microRNA-200 family alterations is related to mesenchymal and drug-resistant phenotypes in human breast cancer cells. Int J Cancer 2010;126(11):2575-2583.
    14 Wellner U, Schubert J, Burk UC, Schmalhofer O, Zhu F, Sonntag A, Waldvogel B, Vannier C, Darling D, zur Hausen A, Brunton VG, Morton J, Sansom O, Schüler J, Stemmler MP, Herzberger C, Hopt U, Keck T, Brabletz S, Brabletz T. The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat Cell Biol 2009;11(12):1487-1495.
    15 Villegas VM, Hess DJ, Wildner A, Gold AS, Murray TG. Retinoblastoma. Curr Opin Ophthalmol 2013;24(6):581-588.
    16 Benavente CA, Dyer MA. Genetics and epigenetics of human retinoblastoma. Annu Rev Pathol 2015;10:547-562.
    17 Yu CL, Tucker MA, Abramson DH, Furukawa K, Seddon JM, Stovall M, Fraumeni JF Jr, Kleinerman RA. Cause-specific mortality in long-term survivors of retinoblastoma. J Nati Cancer Inst 2009;101(8):581-591.
    18 Yan B, Zhang W, Jiang LY, Qin WX, Wang X. Reduced E-cadherin expression is a prognostic biomarker of non-small cell lung cancer: a meta-analysis based on 2395 subjects. Int J Clin Exp Med 2014;7(11): 4352-4356.
    19 Zhang Z, Liu X, Feng B, Liu N, Wu Q, Han Y, Nie Y, Wu K, Shi Y, Fan D. STIM1, a direct target of microRNA-185, promotes tumor metastasis and is associated with poor prognosis in colorectal cancer. Oncogene 2015;34(37):4808-4820.
    20 Huang X, Qian Y, Wu H, Xie X, Zhou Q, Wang Y, Kuang W, Shen L, Li K, Su J, Shen L, Chen X. Aberrant expression of osteopontin and e-cadherin indicates radiation resistance and poor prognosis for patients with cervical carcinoma. J Histochem Cytochem 2015;63(2):88-98.
    21 Han MW, Lee JC, Kim YM, Cha HJ, Roh JL, Choi SH, Nam SY, Cho KJ, Kim SW, Kim SY. Epithelial-mesenchymal transition: clinical implications for nodal metastasis and prognosis of tongue cancer. Otolaryngol Head Neck Surg 2015;152(1):80-86.
    22 Aigner K, Dampier B, Descovich L, Mikula M, Sultan A, Schreiber M, Mikulits W, Brabletz T, Strand D, Obrist P, Sommergruber W, Schweifer N, Wernitznig A, Beug H, Foisner R, Eger A. The transcription factor ZEB1 (deltaEF1) promotes tumour cell dedifferentiation by repressing master regulators of epithelial polarity. Oncogene 2007;26(49):6979-6988.
    23 Bojmar L, Karlsson E, Ellegard S, Olsson H, Björnsson B, Hallböök O, Larsson M, Stål O, Sandström P. The role of microRNA-200 in progression of human colorectal and breast cancer. PLoS One 2013; 8(12):e84815.
    24 Gregory PA, Bracken CP, Smith E, Bert AG, Wright JA, Roslan S, Morris M, Wyatt L, Farshid G, Lim YY, Lindeman GJ, Shannon MF, Drew PA, Khew-Goodall Y, Goodall GJ. An autocrine TGF-beta/ZEB/miR-200 signaling network regulates establishment and maintenance of epithelial-mesenchymal transition. Mol Biol Cell 2011;22(10):1686-1698.
    25 Shields CL, Mashayekhi A, Au AK, Czyz C, Leahey A, Meadows AT, Shields JA. The International Classification of Retinoblastoma predicts chemoreduction success. Ophthalmology 2006;113(12):2276-2280.
    26 Radu OM, Foxwell T, Cieply K, Navina S, Dacic S, Nason KS, Davison JM. HER2 amplification in gastroesophageal adenocarcinoma: correlation of two antibodies using gastric cancer scoring criteria, H score, and digital image analysis with fluorescence in situ hybridization. Am J Clin Pathol 2012;137(4):583-594.
    27 Detre S, Saclani Jotti G, Dowsett M. A "quickscore" method for immunohistochemical semiquantitation: validation for oestrogen receptor in breast carcinomas. J Clin Pathol 1995;48(9):876-878.
    28 Niu K, Shen W, Zhang Y, Zhao Y, Lu Y. MiR-205 promotes motility of ovarian cancer cells via targeting ZEB1. Gene 2015;574(2):330-336.
    29 Kaliki S, Shields CL, Rojanaporn D, Al-Dahmash S, McLaughlin JP, Shields JA, Eagle RC Jr. High-risk retinoblastoma based on international classification of retinoblastoma: analysis of 519 enucleated eyes. Ophthalmology 2013;120(5):997-1003.
    30 Korpal M, Lee ES, Hu G, Kang Y. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J Biol Chem 2008;283(22):14910-14914.
    31 Cochrane DR, Spoelstra NS, Howe EN, Nordeen SK, Richer JK. MicroRNA-200c mitigates invasiveness and restores sensitivity to microtubule-targeting chemotherapeutic agents. Mol Cancer Ther 2009;8(5):1055-1066.
    32 van Roy F, Berx G. The cell-cell adhesion molecule E-cadherin. Cell Mol Life Scie 2008;65(23):3756-3788.
    33 Liang Z, Sun XY, Xu LC, Fu RZ. Abnormal expression of serum soluble E-Cadherin is correlated with clinicopathological features and prognosis of breast cancer. Med Sci Monit 2014;20:2776-2782.
    34 Molina-Ortiz I, Bartolome RA, Hernandez-Varas P, Colo GP, Teixido J. Overexpression of E-cadherin on melanoma cells inhibits chemokine-promoted invasion involving p190RhoGAP/p120ctn-dependent inactivation of RhoA. J Biol Chem 2009;284(22):15147-15157.
    35 Giannoni E, Bianchini F, Masieri L, Serni S, Torre E, Calorini L, Chiarugi P. Reciprocal activation of prostate cancer cells and cancer-associated fibroblasts stimulates epithelial-mesenchymal transition and cancer stemness. Cancer Res 2010;70(17):6945-6956.
    36 Liu S, Tetzlaff MT, Cui R, Xu X. miR-200c inhibits melanoma progression and drug resistance through down-regulation of BMI-1. Am J Pathol 2012;181(15):1823-1835.
    37 Liu L, Qiu M, Tan G, Liang Z, Qin Y, Chen L, Chen H, Liu J. miR-200c inhibits invasion, migration and proliferation of bladder cancer cells through down-regulation of BMI-1 and E2F3. J Transl Med 2014;12:305.
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Xiao-Lei Shao, Yao Chen, Ling Gao. ,/et al.MiR-200c suppresses the migration of retinoblastoma cells by reversing epithelial mesenchymal transition. Int J Ophthalmol, 2017,10(8):1195-1202

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Publication History
  • Received:October 09,2016
  • Revised:April 17,2017
  • Online: August 18,2017