{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T07:28:32Z","timestamp":1778138912062,"version":"3.51.4"},"reference-count":61,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,30]],"date-time":"2024-06-30T00:00:00Z","timestamp":1719705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002632","name":"Hallym University Research Fund 2022","doi-asserted-by":"publisher","award":["HURF-2022-41"],"award-info":[{"award-number":["HURF-2022-41"]}],"id":[{"id":"10.13039\/501100002632","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Post-burn hypertrophic scars often exhibit abnormal pigmentation. Exosomes play important roles in maintaining normal physiological homeostasis and in the pathological development of diseases. This study investigated the effects of the exosomes derived from hypertrophic scar fibroblasts (HTSFs) on melanocytes, which are pigment-producing cells. Normal fibroblasts (NFs) and HTSFs were isolated and cultured from normal skin and hypertrophic scar (HTS) tissue. Both the NF- and HTSF-exosomes were isolated from a cell culture medium and purified using a column-based technique. The normal human epidermal melanocytes were treated with both exosomes at a concentration of 100 \u03bcg\/mL at different times. The cell proliferation, melanin content in the medium, apoptotic factors, transcription factors, melanin synthesis enzymes, signaling, signal transduction pathways, and activators of transcription factors (STAT) 1, 3, 5, and 6 were investigated. Compared with the Dulbecco\u2019s phosphate-buffered saline (DPBS)-treated controls and NF-exosomes, the HTSF-exosomes decreased the melanocyte proliferation and melanin secretion. The molecular patterns of apoptosis, proliferation, melanin synthesis, Smad and non-Smad signaling, and STATs were altered by the treatment with the HTSF-exosomes. No significant differences were observed between the DPBS-treated control and NF-exosome-treated cells. HTSF-derived exosomes may play a role in the pathological epidermal hypopigmentation observed in patients with HTS.<\/jats:p>","DOI":"10.3390\/ijms25137236","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T12:58:42Z","timestamp":1719925122000},"page":"7236","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Exosomes Derived from Hypertrophic Scar Fibroblasts Suppress Melanogenesis in Normal Human Epidermal Melanocytes"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0791-1838","authenticated-orcid":false,"given":"Hui Song","family":"Cui","sequence":"first","affiliation":[{"name":"Burn Institute, Department of Rehabilitation Medicine, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, Seoul 07247, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"So Young","family":"Joo","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, Seoul 07247, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9959-3285","authenticated-orcid":false,"given":"Yoon Soo","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, Seoul 07247, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"You Ra","family":"Lee","sequence":"additional","affiliation":[{"name":"Burn Institute, Department of Rehabilitation Medicine, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, Seoul 07247, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu Mi","family":"Ro","sequence":"additional","affiliation":[{"name":"Burn Institute, Department of Rehabilitation Medicine, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, Seoul 07247, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In Suk","family":"Kwak","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, Seoul 07247, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gi Yeun","family":"Hur","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, Seoul 07247, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4091-6382","authenticated-orcid":false,"given":"Cheong Hoon","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, Seoul 07247, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1016\/S0140-6736(16)31406-4","article-title":"Hypertrophic scarring: The greatest unmet challenge after burn injury","volume":"388","author":"Finnerty","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Koike, S., and Yamasaki, K. (2020). Melanogenesis connection with innate immunity and toll-like receptors. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249769"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e1642","DOI":"10.1097\/GOX.0000000000001642","article-title":"Treatment strategies for hypopigmentation in the context of burn hypertrophic scars","volume":"6","author":"Carney","year":"2018","journal-title":"Plast. Reconstr. Surg. Glob. Open"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1111\/j.1524-475X.2007.00219.x","article-title":"Cellular and molecular pathology of HTS: Basis for treatment","volume":"15","author":"Armour","year":"2007","journal-title":"Wound. Repair Regen."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Cui, H.S., Hong, A.R., Kim, J.B., Yu, J.H., Cho, Y.S., Joo, S.Y., and Seo, C.H. (2018). Extracorporeal shock wave therapy alters the expression of fibrosis-related molecules in fibroblast derived from human hypertrophic scar. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010124"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s41038-015-0026-4","article-title":"The molecular basis of hypertrophic scars","volume":"4","author":"Zhu","year":"2016","journal-title":"Burns Trauma"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1097\/00006534-199810000-00001","article-title":"Transforming growth factor-beta in thermally injured patients with hypertrophic scars: Effects of interferon alpha-2b","volume":"102","author":"Tredget","year":"1998","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1046\/j.1524-475x.2000.00128.x","article-title":"Hypertrophic scar tissues and fibroblasts produce more transforming growth factor-beta1 mRNA and protein than normal skin and cells","volume":"8","author":"Wang","year":"2000","journal-title":"Wound Repair Regen."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1097\/01.prs.0000182343.99694.28","article-title":"Hypertrophic scar fibroblasts have increased connective tissue growth factor expression after transforming growth factor-beta stimulation","volume":"116","author":"Colwell","year":"2005","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1002\/jcp.22454","article-title":"Toll-like receptors expressed by dermal fibroblasts contribute to hypertrophic scarring","volume":"226","author":"Wang","year":"2011","journal-title":"J. Cell. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1097\/00004630-200021020-00010","article-title":"Altered interleukin-6 expression in fibroblasts from hypertrophic burn scars","volume":"21","author":"Xue","year":"2000","journal-title":"J. Burn Care Rehabil."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1152\/physrev.00044.2003","article-title":"Melanin pigmentation in mammalian skin and its hormonal regulation","volume":"84","author":"Slominski","year":"2004","journal-title":"Physiol. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"D\u2019Mello, S.A., Finlay, G.J., Baguley, B.C., and Askarian-Amiri, M.E. (2016). Signaling pathways in melanogenesis. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17071144"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e2308374121","DOI":"10.1073\/pnas.2308374121","article-title":"Photo-neuro-immuno-endocrinology: How the ultraviolet radiation regulates the body, brain, and immune system","volume":"121","author":"Slominski","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1111\/pcmr.12985","article-title":"Participation of keratinocyte- and fibroblast-derived factors in melanocyte homeostasis, the response to UV, and pigmentary disorders","volume":"34","author":"Upadhyay","year":"2021","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.molcel.2008.11.002","article-title":"Inhibition of PAX3 by TGF-\u03b2 modulates melanocyte viability","volume":"32","author":"Yang","year":"2008","journal-title":"Mol. Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1046\/j.1523-1747.2003.12035.x","article-title":"Fibroblast activation protein: Differential expression and serine protease activity in reactive stromal fibroblasts of melanocytic skin tumors","volume":"120","author":"Huber","year":"2003","journal-title":"J. Investig. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1038\/sj.jid.5700629","article-title":"The effects of Dickkopf 1 on gene expression and Wnt signaling by melanocytes: Mechanisms underlying its suppression of melanocyte function and proliferation","volume":"127","author":"Yamaguchi","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"C1757","DOI":"10.1152\/ajpcell.00147.2022","article-title":"Neuroendocrine signaling in the skin with a special focus on the epidermal neuropeptides","volume":"323","author":"Slominski","year":"2022","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/labinvest.2017.9","article-title":"The master role of microphthalmia-associated transcription factor in melanocyte and melanoma biology","volume":"97","author":"Kawakami","year":"2017","journal-title":"Lab. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1083\/jcb.201211138","article-title":"Extracellular vesicles: Exosomes, microvesicles, and friends","volume":"200","author":"Raposo","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.surg.2014.04.014","article-title":"Exosomes mediate intercellular transfer of pro-fibrogenic connective tissue growth factor (CCN2) between hepatic stellate cells, the principal fibrotic cells in the liver","volume":"156","author":"Charrier","year":"2014","journal-title":"Surgery"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1681\/ASN.2012101031","article-title":"TGF-\u03b21-containing exosomes from injured epithelial cells activate fibroblasts to initiate tissue regenerative responses and fibrosis","volume":"24","author":"Borges","year":"2013","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Cui, H.S., Kim, D.H., Joo, S.Y., Cho, Y.S., Kim, J.B., and Seo, C.H. (2022). Exosomes derived from human hypertrophic scar fibroblasts induces smad and TAK1 signaling in normal dermal fibroblasts. Arch. Biochem. Biophys., 722.","DOI":"10.1016\/j.abb.2022.109215"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Cui, H.S., Joo, S.Y., Lee, S.Y., Cho, Y.S., Kim, D.H., and Seo, C.H. (2023). Effect of hypertrophic scar fibroblast-derived exosomes on keratinocytes of normal human skin. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076132"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/jcp.30553","article-title":"The role of exosomes from BALF in lung disease","volume":"237","author":"Liu","year":"2022","journal-title":"J. Cell. Physiol."},{"key":"ref_27","first-page":"5799","article-title":"Downregulation of microRNA-30a in bronchoalveolar lavage fluid from idiopathic pulmonary fibrosis patients","volume":"18","author":"Liu","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1093\/jbcr\/iry045","article-title":"Pigmentation diathesis of hypertrophic scar: An examination of known signaling pathways to elucidate the molecular pathophysiology of injury-related dyschromia","volume":"40","author":"Carney","year":"2019","journal-title":"J. Burn Care Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/j.burns.2019.10.003","article-title":"Hypopigmentation in burns is associated with alterations in the architecture of the skin and the dendricity of the melanocytes","volume":"46","author":"Dutta","year":"2020","journal-title":"Burns"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"664","DOI":"10.2340\/00015555-2080","article-title":"Interferon-gamma inhibits melanogenesis and induces apoptosis in melanocytes: A pivotal role of CD8+ cytotoxic T lymphocytes in vitiligo","volume":"95","author":"Yang","year":"2015","journal-title":"Acta Derm. Venereol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1101\/cshperspect.a008730","article-title":"Inhibitor of apoptosis (IAP) proteins-modulators of cell death and inflammation","volume":"5","author":"Silke","year":"2013","journal-title":"Cold Spring Harb Perspect Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9081","DOI":"10.1073\/pnas.0603114103","article-title":"Interspecies difference in the regulation of melanocyte development by SOX10 and MITF","volume":"103","author":"Hou","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.jdermsci.2016.12.002","article-title":"Sox10 regulates skin melanocyte proliferation by activating the DNA replication licensing factor MCM5","volume":"85","author":"Su","year":"2017","journal-title":"J. Dermatol. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1038\/s41598-024-52629-9","article-title":"Loss of Pax3 causes reduction of melanocytes in the developing mouse cochlea","volume":"14","author":"Udagawa","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Medic, S., and Ziman, M. (2010). PAX3 expression in normal skin melanocytes and melanocytic lesions (naevi and melanomas). PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009977"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Yu, F., Qu, B., Lin, D., Deng, Y., Huang, R., and Zhong, Z. (2018). Pax3 gene regulated melanin synthesis by tyrosinase pathway in Pteria penguin. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19123700"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1093\/hmg\/9.13.1907","article-title":"Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome","volume":"9","author":"Bondurand","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Bartlett, D., Boyle, G.M., Ziman, M., and Medic, S. (2015). Mechanisms contributing to differential regulation of PAX3 downstream target genes in normal human epidermal melanocytes versus melanoma cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0124154"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3426","DOI":"10.1101\/gad.406406","article-title":"Mitf regulation of Dia1 controls melanoma proliferation and invasiveness","volume":"20","author":"Carreira","year":"2006","journal-title":"Genes Dev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1097\/00000478-200101000-00005","article-title":"Microphthalmia transcription factor expression in cutaneous benign, malignant melanocytic, and nonmelanocytic tumors","volume":"25","author":"King","year":"2001","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3813","DOI":"10.1158\/0008-5472.CAN-09-2913","article-title":"Microphthalmia-associated transcription factor controls the DNA damage response and a lineage-specific senescence program in melanomas","volume":"70","author":"Giuliano","year":"2010","journal-title":"Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/0092-8674(93)90429-T","article-title":"Mutations at the mouse microphthalmia locus are associated with defects in a gene encoding a novel basic-helix-loop-helix-zipper protein","volume":"74","author":"Hodgkinson","year":"1993","journal-title":"Cell"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Ballesteros-\u00c1lvarez, J., Dilshat, R., Fock, V., M\u00f6ller, K., Karl, L., Larue, L., \u00d6gmundsd\u00f3ttir, M.H., and Steingr\u00edmsson, E. (2020). MITF and TFEB cross-regulation in melanoma cells. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0238546"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/j.1755-148X.2009.00653.x","article-title":"Fifteen-year quest for microphthalmia-associated transcription factor target genes","volume":"23","author":"Cheli","year":"2010","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/S0092-8674(02)00762-6","article-title":"Bcl2 regulation by the melanocyte master regulator Mitf modulates lineage survival and melanoma cell viability","volume":"109","author":"McGill","year":"2002","journal-title":"Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1038\/nature03269","article-title":"Mitf cooperates with Rb1 and activates p21Cip1 expression to regulate cell cycle progression","volume":"433","author":"Carreira","year":"2005","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.krcp.2012.04.322","article-title":"TGF-\u03b2-activated kinase-1: New insights into the mechanism of TGF-\u03b2 signaling and kidney disease","volume":"31","author":"Kim","year":"2012","journal-title":"Kidney Res. Clin. Pract."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.it.2013.03.007","article-title":"Cell type-specific function of TAK1 in innate immune signaling","volume":"34","author":"Ajibade","year":"2013","journal-title":"Trends Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s12943-015-0338-9","article-title":"MiR-377 targets E2F3 and alters the NF-kB signaling pathway through MAP3K7 in malignant melanoma","volume":"14","author":"Zehavi","year":"2015","journal-title":"Mol. Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"7643","DOI":"10.1002\/jcb.27112","article-title":"Effect of 3,6-anhydro-l-galactose on \u03b1-melanocyte stimulating hormone-induced melanogenesis in human melanocytes and a skin-equivalent model","volume":"119","author":"Kim","year":"2018","journal-title":"J. Cell Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e2250281","DOI":"10.1002\/eji.202250281","article-title":"The IFN-\u03b3-CXCL9\/CXCL10-CXCR3 axis in vitiligo: Pathological mechanism and treatment","volume":"54","author":"Liu","year":"2024","journal-title":"Eur. J. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.jphotobiol.2016.08.024","article-title":"Cross-talk between interferon-gamma and interleukin-18 in melanogenesis","volume":"163","author":"Zhou","year":"2016","journal-title":"J. Photochem. Photobiol. B."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4302","DOI":"10.1074\/jbc.M116.773085","article-title":"Transforming growth factor-\u03b2 (TGF-\u03b2) directly activates the JAK1-STAT3 axis to induce hepatic fibrosis in coordination with the SMAD pathway","volume":"292","author":"Tang","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/jid.2012.331","article-title":"IL-4 inhibits the melanogenesis of normal human melanocytes through the JAK2-STAT6 signaling pathway","volume":"133","author":"Choi","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1089\/jir.2006.26.179","article-title":"Polarized Th2 cytokine production in patients with hypertrophic scar following thermal injury","volume":"26","author":"Tredget","year":"2006","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1111\/j.0022-202X.2005.23772.x","article-title":"Constitutive expression of epidermal growth factor receptors on normal human melanocytes","volume":"125","author":"Mirmohammadsadegh","year":"2005","journal-title":"J. Investig. Dermatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1097\/CMR.0b013e32830ce7d7","article-title":"STAT5 contributes to antiapoptosis in melanoma","volume":"18","author":"Hassel","year":"2008","journal-title":"Melanoma Res."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Hushcha, Y., Blo, I., Oton-Gonzalez, L., Mauro, G.D., Martini, F., Tognon, M., and Mattei, M. (2021). microRNAs in the regulation of melanogenesis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22116104"},{"key":"ref_59","unstructured":"Negrini, M., Calin, G.A., and Croce, C.M. (2022). Pathophysiology roles and translational opportunities of miRNAs in cutaneous melanoma. MicroRNA in Human Malignancies, Academic Press. [1st ed.]. Chapter 26."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Ma, Y., Shen, N., Wicha, M.S., and Luo, M. (2021). The roles of the Let-7 family of microRNAs in the regulation of cancer stemness. Cells, 10.","DOI":"10.3390\/cells10092415"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394Ct Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/7236\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:08:14Z","timestamp":1760108894000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/7236"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,30]]},"references-count":61,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["ijms25137236"],"URL":"https:\/\/doi.org\/10.3390\/ijms25137236","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,30]]}}}