Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
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SH3BP4, a novel pigmentation gene, is inversely regulated by miR-125b and MITF

  • Kim, Kyu-Han (Basic Research & Innovation Division, R&D Unit, AmorePacific Corporation) ;
  • Lee, Tae Ryong (Basic Research & Innovation Division, R&D Unit, AmorePacific Corporation) ;
  • Cho, Eun-Gyung (Basic Research & Innovation Division, R&D Unit, AmorePacific Corporation)
  • Received : 2016.08.16
  • Accepted : 2017.03.05
  • Published : 2017.08.31
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Abstract

Our previous work has identified miR-125b as a negative regulator of melanogenesis. However, the specific melanogenesis-related genes targeted by this miRNA had not been identified. In this study, we established a screening strategy involving three consecutive analytical approaches-analysis of target genes of miR-125b, expression correlation analysis between each target gene and representative pigmentary genes, and functional analysis of candidate genes related to melanogenesis-to discover melanogenesis-related genes targeted by miR-125b. Through these analyses, we identified SRC homology 3 domain-binding protein 4 (SH3BP4) as a novel pigmentation gene. In addition, by combining bioinformatics analysis and experimental validation, we demonstrated that SH3BP4 is a direct target of miR-125b. Finally, we found that SH3BP4 is transcriptionally regulated by microphthalmia-associated transcription factor as its direct target. These findings provide important insights into the roles of miRNAs and their targets in melanogenesis.

Keywords

References

  1. Kobayashi N, Nakagawa A, Muramatsu T, Yamashina Y, Shirai T, Hashimoto MW et al. Supranuclear melanin caps reduce ultraviolet induced DNA photoproducts in human epidermis. J Invest Dermatol 1998; 110: 806-810. https://doi.org/10.1046/j.1523-1747.1998.00178.x
  2. Meredith P, Sarna T. The physical and chemical properties of eumelanin. Pigment Cell Res 2006; 19: 572-594. https://doi.org/10.1111/j.1600-0749.2006.00345.x
  3. d'Ischia M, Wakamatsu K, Cicoira F, Di Mauro E, Garcia-Borron JC, Commo S et al. Melanins and melanogenesis: from pigment cells to human health and technological applications. Pigment Cell Melanoma Res 2015; 28: 520-544. https://doi.org/10.1111/pcmr.12393
  4. Huntzinger E, Izaurralde E. Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nat Rev Genet 2011; 12: 99-110. https://doi.org/10.1038/nrg2936
  5. Kim KH, Bin BH, Kim J, Dong SE, Park PJ, Choi H et al. Novel inhibitory function of miR-125b in melanogenesis. Pigment Cell Melanoma Res 2014; 27: 140-144. https://doi.org/10.1111/pcmr.12179
  6. Banzhaf-Strathmann J, Edbauer D. Good guy or bad guy: the opposing roles of microRNA 125b in cancer. Cell Commun Signal 2014; 12: 30. https://doi.org/10.1186/1478-811X-12-30
  7. Choi H, Ahn S, Lee BG, Chang I, Hwang JS. Inhibition of skin pigmentation by an extract of Lepidium apetalum and its possible implication in IL-6 mediated signaling. Pigment Cell Res 2005; 18: 439-446.
  8. Yang JH, Li JH, Shao P, Zhou H, Chen YQ, Qu LH. starBase: a database for exploring microRNA-mRNA interaction maps from Argonaute CLIP-Seq and Degradome-Seq data. Nucleic Acids Res 2011; 39(Database issue): D202-D209. https://doi.org/10.1093/nar/gkq1056
  9. Li JH, Liu S, Zhou H, Qu LH, Yang JH. starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res 2014; 42(Database issue): D92-D97. https://doi.org/10.1093/nar/gkt1248
  10. Webster DE, Barajas B, Bussat RT, Yan KJ, Neela PH, Flockhart RJ et al. Enhancer-targeted genome editing selectively blocks innate resistance to oncokinase inhibition. Genome Res 2014; 24: 751-760. https://doi.org/10.1101/gr.166231.113
  11. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 2005; 102: 15545-15550. https://doi.org/10.1073/pnas.0506580102
  12. Praetorius C, Grill C, Stacey SN, Metcalf AM, Gorkin DU, Robinson KC et al. A polymorphism in IRF4 affects human pigmentation through a tyrosinase-dependent MITF/TFAP2A pathway. Cell 2013; 155: 1022-1033. https://doi.org/10.1016/j.cell.2013.10.022
  13. So AY, Sookram R, Chaudhuri AA, Minisandram A, Cheng D, Xie C et al. Dual mechanisms by which miR-125b represses IRF4 to induce myeloid and B-cell leukemias. Blood 2014; 124: 1502-1512.
  14. Mort RL, Jackson IJ, Patton EE. The melanocyte lineage in development and disease. Development 2015; 142: 620-632. https://doi.org/10.1242/dev.106567
  15. Shoag J, Haq R, Zhang M, Liu L, Rowe GC, Jiang A et al. PGC-1 coactivators regulate MITF and the tanning response. Mol Cell 2013; 49: 145-157. https://doi.org/10.1016/j.molcel.2012.10.027
  16. Yamaguchi Y, Hearing VJ. Physiological factors that regulate skin pigmentation. Biofactors 2009; 35: 193-199. https://doi.org/10.1002/biof.29
  17. Tosoni D, Puri C, Confalonieri S, Salcini AE, De Camilli P, Tacchetti C et al. TTP specifically regulates the internalization of the transferrin receptor. Cell 2005; 123: 875-888. https://doi.org/10.1016/j.cell.2005.10.021
  18. Chapuy B, Tikkanen R, Muhlhausen C, Wenzel D, von Figura K, Honing S. AP-1 and AP-3 mediate sorting of melanosomal and lysosomal membrane proteins into distinct post-Golgi trafficking pathways. Traffic 2008; 9: 1157-1172. https://doi.org/10.1111/j.1600-0854.2008.00745.x
  19. Delevoye C, Hurbain I, Tenza D, Sibarita JB, Uzan-Gafsou S, Ohno H et al. AP-1 and KIF13A coordinate endosomal sorting and positioning during melanosome biogenesis. J Cell Biol 2009; 187: 247-264. https://doi.org/10.1083/jcb.200907122
  20. Bultema JJ, Ambrosio AL, Burek CL, Di Pietro SM. BLOC-2, AP-3, and AP-1 proteins function in concert with Rab38 and Rab32 proteins to mediate protein trafficking to lysosome-related organelles. J Biol Chem 2012; 287: 19550-19563. https://doi.org/10.1074/jbc.M112.351908
  21. Kim YM, Stone M, Hwang TH, Kim YG, Dunlevy JR, Griffin TJ et al. SH3BP4 is a negative regulator of amino acid-Rag GTPase-mTORC1 signaling. Mol Cell 2012; 46: 833-846. https://doi.org/10.1016/j.molcel.2012.04.007
  22. Ho H, Kapadia R, Al-Tahan S, Ahmad S, Ganesan AK. WIPI1 coordinates melanogenic gene transcription and melanosome formation via TORC1 inhibition. J Biol Chem 2011; 286: 12509-12523. https://doi.org/10.1074/jbc.M110.200543
  23. Hah YS, Cho HY, Lim TY, Park DH, Kim HM, Yoon J et al. Induction of melanogenesis by rapamycin in human MNT-1 melanoma cells. Ann Dermatol 2012; 24: 151-157. https://doi.org/10.5021/ad.2012.24.2.151
  24. Huang K, Fingar DC. Growing knowledge of the mTOR signaling network. Semin Cell Dev Biol 2014; 36: 79-90. https://doi.org/10.1016/j.semcdb.2014.09.011

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