{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T17:01:21Z","timestamp":1784912481903,"version":"3.55.0"},"reference-count":36,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:00:00Z","timestamp":1747180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32060781"],"award-info":[{"award-number":["32060781"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["JJKH20220543KJ"],"award-info":[{"award-number":["JJKH20220543KJ"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jilin Provincial Department of Education Foundation Program","award":["32060781"],"award-info":[{"award-number":["32060781"]}]},{"name":"Jilin Provincial Department of Education Foundation Program","award":["JJKH20220543KJ"],"award-info":[{"award-number":["JJKH20220543KJ"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The proliferation and maturation of hair follicles in follicular papilla cells are predominantly governed by miRNAs, which significantly influence the cell cycle, apoptosis, and proliferation. miR-370-3p has been associated with several biological processes and targets SMAD4, a crucial component in hair follicle development. Tissue expression profiling revealed significant differences in miR-370-3p levels between skin tissues of the two sheep breeds in January and October, as well as between tissues of the Xinji fine-wool sheep and Small-tail Han sheep. SMAD4 exhibited significant differences in tissue-specific expression in the heart, spleen, skin, lungs, and muscles from Xinji fine-wool sheep and Small-tail Han sheep. Bioinformatics analysis and dual-luciferase reporter assays validated the regulatory interaction between miR-370-3p and SMAD4. CCK-8 experiments demonstrated that miR-370-3p\u2019s targeting of SMAD4 suppressed cell growth. Cell cycle analysis demonstrated that miR-370-3p\u2019s targeting of SMAD4 influenced the cell cycle. Annexin V-FITC\/PI dual labeling demonstrated that miR-370-3p\u2019s targeting of SMAD4 promoted cell apoptosis. RT-qPCR data demonstrated that miR-370-3p\u2019s targeting of SMAD4 elevated the expression of JUN, c-MYC, and TCF7L2 while suppressing \u03b2-catenin expression. Western blot (WB) analysis demonstrated that miR-370-3p targeting of SMAD4 significantly promoted c-MYC expression while inhibiting CCND1, CCND2, and \u03b2-catenin expression. miR-370-3p and SMAD4 exhibit spatiotemporal expression differences in sheep skin tissues, with widespread expression across various tissues. Furthermore, it confirmed that miR-370-3p targets SMAD4 to inhibit follicular papilla cell proliferation, promote apoptosis, and influence the cell cycle.<\/jats:p>","DOI":"10.3390\/cells14100714","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T10:27:41Z","timestamp":1747218461000},"page":"714","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["miR-370-3p Inhibited the Proliferation of Sheep Dermal Papilla Cells by Inhibiting the Expression of SMAD4"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7625-2251","authenticated-orcid":false,"given":"Jiaqi","family":"Fu","sequence":"first","affiliation":[{"name":"College of Agriculture, Yanbian University, Yanji 133002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Agriculture, Yanbian University, Yanji 133002, China"},{"name":"Animal Disease Prevention and Control Center of Panshi City, Panshi 132300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqing","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Agriculture, Yanbian University, Yanji 133002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Qi","sequence":"additional","affiliation":[{"name":"College of Agriculture, Yanbian University, Yanji 133002, China"},{"name":"Animal Biotechnology Institute, Jilin Academy of Agricultural Sciences, Gongzhuling 136100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caihong","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Agriculture, Yanbian University, Yanji 133002, China"},{"name":"Animal Biotechnology Institute, Jilin Academy of Agricultural Sciences, Gongzhuling 136100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huansong","family":"Li","sequence":"additional","affiliation":[{"name":"College of Agriculture, Yanbian University, Yanji 133002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinshun","family":"Cai","sequence":"additional","affiliation":[{"name":"College of Agriculture, Yanbian University, Yanji 133002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Ji","sequence":"additional","affiliation":[{"name":"College of Agriculture, Yanbian University, Yanji 133002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lichun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Animal Biotechnology Institute, Jilin Academy of Agricultural Sciences, Gongzhuling 136100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuliang","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Agriculture, Yanbian University, Yanji 133002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1089\/ten.teb.2021.0098","article-title":"Hair Follicle Stem Cells for Tissue Regeneration","volume":"28","author":"Peterson","year":"2022","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lin, X., Zhu, L., and He, J. (2022). Morphogenesis, Growth Cycle and Molecular Regulation of Hair Follicles. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.899095"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3869","DOI":"10.1096\/fj.10-160663","article-title":"Micro-RNA-31 controls hair cycle-associated changes in gene expression programs of the skin and hair follicle","volume":"24","author":"Mardaryev","year":"2010","journal-title":"FASEB J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.cell.2009.01.002","article-title":"MicroRNAs: Target recognition and regulatory functions","volume":"136","author":"Bartel","year":"2009","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Yan, S., and Jiao, K. (2016). Functions of miRNAs during Mammalian Heart Development. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17050789"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Cao, L., Tian, T., Huang, Y., Tao, S., Zhu, X., Yang, M., Gu, J., Feng, G., Ma, Y., and Xia, R. (2021). Neural progenitor cell-derived nanovesicles promote hair follicle growth via miR-100. J. Nanobiotechnology, 19.","DOI":"10.1186\/s12951-020-00757-5"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"20329","DOI":"10.1002\/jcp.28633","article-title":"miR-218-5p regulates skin and hair follicle development through Wnt\/\u03b2-catenin signaling pathway by targeting SFRP2","volume":"234","author":"Zhao","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1093\/jmcb\/mjy051","article-title":"A role for the Tgf-\u03b2\/Bmp co-receptor Endoglin in the molecular oscillator that regulates the hair follicle cycle","volume":"11","author":"Carrasco","year":"2019","journal-title":"J. Mol. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.ydbio.2008.07.020","article-title":"SMAD4-dependent desmoglein-4 expression contributes to hair follicle integrity","volume":"322","author":"Owens","year":"2008","journal-title":"Dev. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/sj.jid.5700969","article-title":"The role of Smads in skin development","volume":"128","author":"Owens","year":"2008","journal-title":"J. Investig. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1091\/mbc.e08-07-0731","article-title":"Disruption of SMAD4 in mouse epidermis leads to depletion of follicle stem cells","volume":"20","author":"Yang","year":"2009","journal-title":"Mol. Biol. Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1002\/ar.24480","article-title":"miR-203a-3p promotes loureirin A-induced hair follicle stem cells differentiation by targeting Smad1","volume":"304","author":"Luo","year":"2021","journal-title":"Anat. Rec. Hoboken"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Li, J., Zhao, B., Yao, S., Dai, Y., Zhang, X., Yang, N., Bao, Z., Cai, J., Chen, Y., and Wu, X. (2023). Dermal PapillaCell-Derived Exosomes Regulate Hair Follicle Stem Cell Proliferation via LEF1. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043961"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Rendl, M., Lewis, L., and Fuchs, E. (2005). Molecular dissection of mesenchymal-epithelial interactions in the hair follicle. PLoS Biol., 3.","DOI":"10.1371\/journal.pbio.0030331"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/nrm2868","article-title":"MicroRNA control of signal transduction","volume":"11","author":"Inui","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nrg2936","article-title":"Gene silencing by microRNAs: Contributions of translational repression and mRNA decay","volume":"12","author":"Huntzinger","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8289","DOI":"10.1002\/cam4.5527","article-title":"Circular RNA hsa_circ_0004689 (circSWT1) promotes NSCLC progression via the miR-370-3p\/SNAIL axis by inducing cell epithelial-mesenchymal transition (EMT)","volume":"12","author":"Long","year":"2023","journal-title":"Cancer Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Wang, P., Zhang, H., Zhao, W., and Dai, N. (2021). Silencing of long non-coding RNA KCNQ1OT1 alleviates LPS-induced lung injury by regulating the miR-370-3p\/FOXM1 axis in childhood pneumonia. BMC Pulm. Med., 21.","DOI":"10.1186\/s12890-021-01609-0"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Yanni, J., D\u2019Souza, A., Wang, Y., Li, N., Hansen, B.J., Zakharkin, S.O., Smith, M., Hayward, C., Whitson, B.A., and Mohler, P.J. (2020). Silencing miR-370-3p rescues funny current and sinus node function in heart failure. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-67790-0"},{"key":"ref_20","first-page":"94","article-title":"CircCCNB1 Knockdown Blocks the Progression of Cervical Cancer by Acting as Competing Endogenous RNA in the miR-370-3p\/SOX4 Pathway","volume":"53","author":"Jia","year":"2023","journal-title":"Ann. Clin. Lab. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ma, H., Qu, S., Zhai, Y., and Yang, X. (2022). circ_0025033 promotes ovarian cancer development via regulating the hsa_miR-370-3p\/SLC1A5 axis. Cell. Mol. Biol. Lett., 27.","DOI":"10.1186\/s11658-022-00364-2"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5123","DOI":"10.7150\/ijbs.66673","article-title":"Decrease of circARID1A retards glioblastoma invasion by modulating miR-370-3p\/ TGFBR2 pathway","volume":"18","author":"Li","year":"2022","journal-title":"Int. J. Biol. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"145339","DOI":"10.1016\/j.gene.2020.145339","article-title":"Characterization and functional analysis of SMAD2 regulation in hair follicle cycle in Angora rabbits","volume":"770","author":"Bao","year":"2021","journal-title":"Gene"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"151603","DOI":"10.1016\/j.acthis.2020.151603","article-title":"All-trans-retinoic acid inhibits mink hair follicle growth via inhibiting proliferation and inducing apoptosis of dermal papilla cells through TGF-\u03b22\/Smad2\/3 pathway","volume":"122","author":"Nan","year":"2020","journal-title":"Acta Histochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.devcel.2006.06.014","article-title":"Smad7-induced beta-catenin degradation alters epidermal appendage development","volume":"11","author":"Han","year":"2006","journal-title":"Dev. Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/j.bbrc.2016.01.148","article-title":"Protopanaxatirol type ginsenoside Re promotes cyclic growth of hair follicles via inhibiting transforming growth factor \u03b2 signaling cascades","volume":"470","author":"Li","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1002\/pmic.200700760","article-title":"The up-regulation of 14-3-3 proteins in SMAD4 deficient epidermis and hair follicles at catagen","volume":"8","author":"Yuan","year":"2008","journal-title":"Proteomics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8671","DOI":"10.1158\/0008-5472.CAN-05-0800","article-title":"Targeted disruption of SMAD4 in mouse epidermis results in failure of hair follicle cycling and formation of skin tumors","volume":"65","author":"Yang","year":"2005","journal-title":"Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e48693","DOI":"10.15252\/embr.201948693","article-title":"Wip1 regulates SMAD4 phosphorylation and inhibits TGF-\u03b2 signaling","volume":"21","author":"Park","year":"2020","journal-title":"EMBO Rep."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Wang, Z., Zhao, X., Ma, Z., Liu, L., Wang, B., and Li, Y. (2018). WITHDRAWN: Modulation on gallbladder carcinoma by TGF-\u03b21 via IGFBP-2. Cancer Biomark.","DOI":"10.3233\/CBM-181895"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5210","DOI":"10.1016\/j.csbj.2021.09.009","article-title":"Conformational landscape of multidomain SMAD proteins","volume":"19","author":"Gomes","year":"2021","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"jkab091","DOI":"10.1093\/g3journal\/jkab091","article-title":"Chi-miR-370-3p regulates hair follicle morphogenesis of Inner Mongolian cashmere goats","volume":"11","author":"Hai","year":"2021","journal-title":"G3 Bethesda"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/s41419-020-2578-x","article-title":"SMAD4 activates Wnt signaling pathway to inhibit granulosa cell apoptosis","volume":"11","author":"Du","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1158\/1541-7786.MCR-20-0721","article-title":"Colorectal Cancer-Associated SMAD4 R361 Hotspot Mutations Boost Wnt\/\u03b2-Catenin Signaling through Enhanced SMAD4-LEF1 Binding","volume":"19","author":"Lanauze","year":"2021","journal-title":"Mol. Cancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"dev199984","DOI":"10.1242\/dev.199984","article-title":"SMAD4 controls proliferation of interstitial cells in the neonatal kidney","volume":"149","author":"McCarthy","year":"2022","journal-title":"Development"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/bjc.2014.560","article-title":"The BMP pathway either enhances or inhibits the Wnt pathway depending on the SMAD4 and p53 status in CRC","volume":"112","author":"Voorneveld","year":"2015","journal-title":"Br. J. Cancer"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/10\/714\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:32:43Z","timestamp":1760031163000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/10\/714"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,14]]},"references-count":36,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["cells14100714"],"URL":"https:\/\/doi.org\/10.3390\/cells14100714","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,14]]}}}