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MiR-361-5p inhibits cell proliferation and induces cell apoptosis in retinoblastoma by negatively regulating CLDN8

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Abstract

Purpose

MiR-361-5p has been reported to act as tumor suppressor in several types of cancers. Retinoblastoma (RB) is the most common ocular tumor in childhood. The current study aimed to investigate the expression pattern and biological function of miR-361-5p in RB.

Methods

Quantitative real time was utilized to determine and compare the expression of miR-361-5p in RB cells and normal retinal pigment epithelial cell line ARPE-19. CCK-8 and Edu assay were performed to assess cell proliferation. Cell apoptosis was evaluated using flow cytometry assay. Bioinformatics databases and luciferase reporter assay were applied to predict and confirm the target gene of miR-361-5p in RB cells.

Results

Here, we found miR-361-5p was significantly downregulated in RB cells compared with normal retinal pigment epithelial cell line ARPE-19. MiR-361-5p overexpression significantly inhibited or silencing promoted cell proliferation in Y79 and SO-RB50 cells, respectively. Flow cytometry assay showed a significantly decreased cell apoptosis in miR-361-5p silencing Y79 cells and increased cell apoptosis in miR-361-5p overexpressing SO-RB50 cells. Moreover, miR-361-5p directly bound to the 3′ untranslated region of claudin 8 (CLDN8) and inhibited the expression of CLDN8. Furthermore, we found knockdown of CLDN8 photocopied the effect of miR-361-5p on cell proliferation and apoptosis in RB cells.

Conclusion

These results indicated that overexpression of miR-361-5p might act as a suppressor in RB by targeting CLDN8 to inhibit the cellular function.

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References

  1. Fernandes AG, Pollock BD, Rabito FA (2018) Retinoblastoma in the United States: a 40-year incidence and survival analysis. J Pediatr Ophthalmol Strabismus 55:182–188. https://doi.org/10.3928/01913913-20171116-03

    Article  PubMed  Google Scholar 

  2. Theriault BL, Dimaras H, Gallie BL, Corson TW (2014) The genomic landscape of retinoblastoma: a review. Clin Exp Ophthalmol 42:33–52. https://doi.org/10.1111/ceo.12132

    Article  PubMed  Google Scholar 

  3. Li WL, Buckley J, Sanchez-Lara PA, Maglinte DT, Viduetsky L, Tatarinova TV, Aparicio JG, Kim JW, Au M, Ostrow D, Lee TC, O’Gorman M, Judkins A, Cobrinik D, Triche TJ (2016) A rapid and sensitive next-generation sequencing method to detect RB1 mutations improves care for retinoblastoma patients and their families. J Mol Diagn 18:480–493. https://doi.org/10.1016/j.jmoldx.2016.02.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Dimaras H, Corson TW, Cobrinik D, White A, Zhao J, Munier FL, Abramson DH, Shields CL, Chantada GL, Njuguna F, Gallie BL (2015) Retinoblastoma. Nature Reviews Disease Primers 1:15021. https://doi.org/10.1038/nrdp.2015.21 https://www.nature.com/articles/nrdp201521#supplementary-information

    Article  PubMed  PubMed Central  Google Scholar 

  5. Nishikawa R, Chiyomaru T, Enokida H, Inoguchi S, Ishihara T, Matsushita R, Goto Y, Fukumoto I, Nakagawa M, Seki N (2015) Tumour-suppressive microRNA-29s directly regulate LOXL2 expression and inhibit cancer cell migration and invasion in renal cell carcinoma. FEBS Lett 589:2136–2145. https://doi.org/10.1016/j.febslet.2015.06.005

    Article  CAS  PubMed  Google Scholar 

  6. Desvignes T, Batzel P, Berezikov E, Eilbeck K, Eppig JT, McAndrews MS, Singer A, Postlethwait JH (2015) miRNA nomenclature: a view incorporating genetic origins, biosynthetic pathways, and sequence variants. Trends Genet 31:613–626. https://doi.org/10.1016/j.tig.2015.09.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Wilczynska A, Bushell M (2015) The complexity of miRNA-mediated repression. Cell Death Differ 22:22–33. https://doi.org/10.1038/cdd.2014.112

    Article  CAS  PubMed  Google Scholar 

  8. Oliveto S, Mancino M, Manfrini N, Biffo S (2017) Role of microRNAs in translation regulation and cancer. World J Biol Chem 8:45–56. https://doi.org/10.4331/wjbc.v8.i1.45

    Article  PubMed  PubMed Central  Google Scholar 

  9. Acunzo M, Romano G, Wernicke D, Croce CM (2015) MicroRNA and cancer--a brief overview. Adv Biol Regul 57:1–9. https://doi.org/10.1016/j.jbior.2014.09.013

    Article  CAS  PubMed  Google Scholar 

  10. Ma F, Song H, Guo B, Zhang Y, Zheng Y, Lin C, Wu Y, Guan G, Sha R, Zhou Q, Wang D, Zhou X, Li J, Qiu X (2015) MiR-361-5p inhibits colorectal and gastric cancer growth and metastasis by targeting staphylococcal nuclease domain containing-1. Oncotarget 6:17404–17416. https://doi.org/10.18632/oncotarget.3744

    Article  PubMed  PubMed Central  Google Scholar 

  11. Liu D, Tao T, Xu B, Chen S, Liu C, Zhang L, Lu K, Huang Y, Jiang L, Zhang X, Huang X, Zhang L, Han C, Chen M (2014) MiR-361-5p acts as a tumor suppressor in prostate cancer by targeting signal transducer and activator of transcription-6(STAT6). Biochem Biophys Res Commun 445:151–156. https://doi.org/10.1016/j.bbrc.2014.01.140

    Article  CAS  PubMed  Google Scholar 

  12. Hou XW, Sun X, Yu Y, Zhao HM, Yang ZJ, Wang X, Cao XC (2017) miR-361-5p suppresses lung cancer cell lines progression by targeting FOXM1. Neoplasma 64:526–534. https://doi.org/10.4149/neo_2017_406

    Article  CAS  PubMed  Google Scholar 

  13. Zhang X, Shao R, Gao W, Sun G, Liu Y, Fa X (2018) Inhibition of miR-361-5p suppressed pulmonary artery smooth muscle cell survival and migration by targeting ABCA1 and inhibiting the JAK2/STAT3 pathway. Exp Cell Res 363:255–261. https://doi.org/10.1016/j.yexcr.2018.01.015

    Article  CAS  PubMed  Google Scholar 

  14. Haseloff RF, Dithmer S, Winkler L, Wolburg H, Blasig IE (2015) Transmembrane proteins of the tight junctions at the blood-brain barrier: structural and functional aspects. Semin Cell Dev Biol 38:16–25. https://doi.org/10.1016/j.semcdb.2014.11.004

    Article  CAS  Google Scholar 

  15. Tsukita S, Furuse M, Itoh M (2001) Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol 2:285–293. https://doi.org/10.1038/35067088

    Article  CAS  PubMed  Google Scholar 

  16. Ouban A, Ahmed AA (2010) Claudins in human cancer: a review. Histol Histopathol 25:83–90. https://doi.org/10.14670/HH-25.83

    Article  CAS  PubMed  Google Scholar 

  17. Jauregi-Miguel A, Fernandez-Jimenez N, Irastorza I, Plaza-Izurieta L, Vitoria JC, Bilbao JR (2014) Alteration of tight junction gene expression in celiac disease. J Pediatr Gastroenterol Nutr 58:762–767. https://doi.org/10.1097/MPG.0000000000000338

    Article  CAS  PubMed  Google Scholar 

  18. Lerner A, Matthias T (2015) Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease. Autoimmun Rev 14:479–489. https://doi.org/10.1016/j.autrev.2015.01.009

    Article  CAS  Google Scholar 

  19. Landy J, Ronde E, English N, Clark SK, Hart AL, Knight SC, Ciclitira PJ, Al-Hassi HO (2016) Tight junctions in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer. World J Gastroenterol 22:3117–3126. https://doi.org/10.3748/wjg.v22.i11.3117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Singh AB, Dhawan P (2015) Claudins and cancer: fall of the soldiers entrusted to protect the gate and keep the barrier intact. Semin Cell Dev Biol 42:58–65. https://doi.org/10.1016/j.semcdb.2015.05.001

    Article  CAS  Google Scholar 

  21. Xu J, Yang Y, Hao P, Ding X (2015) Claudin 8 contributes to malignant proliferation in human osteosarcoma U2OS cells. Cancer Biother Radiopharm 30:400–404. https://doi.org/10.1089/cbr.2015.1815

    Article  CAS  PubMed  Google Scholar 

  22. Ashikari D, Takayama KI, Obinata D, Takahashi S, Inoue S (2017) CLDN8, an androgen-regulated gene, promotes prostate cancer cell proliferation and migration. Cancer Sci 108:1386–1393. https://doi.org/10.1111/cas.13269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Mataki H, Enokida H, Chiyomaru T, Mizuno K, Matsushita R, Goto Y, Nishikawa R, Higashimoto I, Samukawa T, Nakagawa M, Inoue H, Seki N (2015) Downregulation of the microRNA-1/133a cluster enhances cancer cell migration and invasion in lung-squamous cell carcinoma via regulation of Coronin1C. J Hum Genet 60:53–61. https://doi.org/10.1038/jhg.2014.111

    Article  CAS  PubMed  Google Scholar 

  24. Kanitz A, Imig J, Dziunycz PJ, Primorac A, Galgano A, Hofbauer GF, Gerber AP, Detmar M (2012) The expression levels of microRNA-361-5p and its target VEGFA are inversely correlated in human cutaneous squamous cell carcinoma. PLoS One 7:e49568. https://doi.org/10.1371/journal.pone.0049568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Tsukita S, Tanaka H, Tamura A (2019) The claudins: from tight junctions to biological systems. Trends Biochem Sci 2018. https://doi.org/10.1016/j.tibs.2018.09.008

  26. Van Itallie CM, Colegio OR, Anderson JM (2004) The cytoplasmic tails of claudins can influence tight junction barrier properties through effects on protein stability. J Membr Biol 199:29–38

    Article  CAS  PubMed  Google Scholar 

  27. Van Itallie CM, Anderson JM (2014) Architecture of tight junctions and principles of molecular composition. Semin Cell Dev Biol 36:157–165. https://doi.org/10.1016/j.semcdb.2014.08.011

    Article  CAS  Google Scholar 

  28. Gonzalez-Mariscal L, Miranda J, Raya-Sandino A, Dominguez-Calderon A, Cuellar-Perez F (2017) ZO-2, a tight junction protein involved in gene expression, proliferation, apoptosis, and cell size regulation. Ann N Y Acad Sci 1397:35–53. https://doi.org/10.1111/nyas.13334

    Article  CAS  PubMed  Google Scholar 

  29. Cordenonsi M (2015) ZO-oming on growth control by junctional proteins. Cell Cycle 14:472. https://doi.org/10.1080/15384101.2015.1006557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Chidiac R, Zhang Y, Tessier S, Faubert D, Delisle C, Gratton JP (2016) Comparative phosphoproteomics analysis of VEGF and angiopoietin-1 signaling reveals ZO-1 as a critical regulator of endothelial cell proliferation. Mol Cell Proteomics 15:1511–1525. https://doi.org/10.1074/mcp.M115.053298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Bai L, Mao R, Wang J, Ding L, Jiang S, Gao C, Kang H, Chen X, Sun X, Xu J (2015) ERK1/2 promoted proliferation and inhibited apoptosis of human cervical cancer cells and regulated the expression of c-Fos and c-Jun proteins. Med Oncol 32:57. https://doi.org/10.1007/s12032-015-0490-5

    Article  CAS  PubMed  Google Scholar 

  32. Lawlor MA, Alessi DR:2001 PKB/Akt. A key mediator of cell proliferation, survival and insulin responses? , 114:2903–2910

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Correspondence to Weiwei Kuang.

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Liu, B., Lu, B., Wang, X. et al. MiR-361-5p inhibits cell proliferation and induces cell apoptosis in retinoblastoma by negatively regulating CLDN8. Childs Nerv Syst 35, 1303–1311 (2019). https://doi.org/10.1007/s00381-019-04199-9

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  • DOI: https://doi.org/10.1007/s00381-019-04199-9

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