Kim, K. Y. Hwang, Y. J. Jung, M-K Choe, J. Kim, Y. Kim, S. Lee, C-J Ahn, H. Lee, J. Kowall, N. W. Kim, Y. K. Kim, J-I Lee, S. B. Ryu, H. 2024-01-20T10:34:59Z 2024-01-20T10:34:59Z 2021-09-05 2014-01 1350-9047 https://pubs.kist.re.kr/handle/201004/127285 EWS (Ewing's Sarcoma) gene encodes an RNA/DNA-binding protein that is ubiquitously expressed and involved in various cellular processes. EWS deficiency leads to impaired development and early senescence through unknown mechanisms. We found that EWS regulates the expression of Drosha and microRNAs (miRNAs). EWS deficiency resulted in increased expression of Drosha, a well-known microprocessor, and increased levels of miR-29b and miR-18b. Importantly, miR-29b and miR-18b were directly involved in the post-transcriptional regulation of collagen IV alpha 1 (CoI4a1) and connective tissue growth factor (CTGF) in EWS knock-out (KO) mouse embryonic fibroblast cells. The upregulation of Drosha, miR-29b and miR-18b and the sequential downregulation of CoI4a1 and CTGF contributed to the deregulation of dermal development in EWS KO mice. Otherwise, knockdown of Drosha rescued miRNA-dependent downregulation of CoI4a1 and CTGF proteins. Taken together, our data indicate that EWS is involved in post-transcriptional regulation of CoI4a1 and CTGF via a Drosha-miRNA-dependent pathway. This finding suggests that EWS has a novel role in dermal morphogenesis through the modulation of miRNA biogenesis. English NATURE PUBLISHING GROUP TISSUE GROWTH-FACTOR SARCOMA GENE EWS COLLAGEN-IV COMPLEX A multifunctional protein EWS regulates the expression of Drosha and microRNAs Article 10.1038/cdd.2013.144 1 CELL DEATH AND DIFFERENTIATION, v.21, no.1, pp.136 - 145 CELL DEATH AND DIFFERENTIATION 21 1 136 145 scie scopus 000328622100015 2-s2.0-84890116155 Biochemistry & Molecular Biology Cell Biology Biochemistry & Molecular Biology Cell Biology Article TISSUE GROWTH-FACTOR SARCOMA GENE EWS COLLAGEN-IV COMPLEX EWS Drosha microRNA CTGF dermal development