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. 2022 Aug 8;12:13550. doi: 10.1038/s41598-022-17767-y

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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miRNA-125b from WJ-EV was involved the downregulation of the expression of HIF1α in wBCC. (A) The miRNAs related to the expression of HIF1α were analyzed by t-Distributed Stochastic Neighbor Embedding (t-SNE). (B) The expression of miRNAs related to the HIF1α expression in BCC and wBCC was presented in a 3-dimensional plot. (C) The expression of miRNAs related to HIF1α in BCC and wBCC. (D) Screening results of target genes which directly regulated by miRNAs related to HIF1α in BCC and wBCC, from a miRNA database, miRDB (http://mirdb.org/). Red color indicate anti-HIF1α (HIF1α-AN). A zoom-in image of target genes were shown in Supplementary Fig. S5. (E) HIF1α gene expression of BCC and wBCC, n = 6, **p < 0.01. (F) HIF1α protein expression in BCC and wBCC, n = 3, ***p < 0.001. N: normoxia, H: hypoxia. Full-length blots were shown in Supplementary Fig. S6. (G) The expression of miR-125b in BCC and wBCC, n = 3, *p < 0.05. (H) The gene expression of HIF1α in BCC, BCC with the overexpression of miR125b (treated with 50 nM of mimics of miR125b), wBCC, and wBCC with the inhibition of miR125b (treated with 25 nM of inhibitor of miR125b), n = 6, **p < 0.01. (I) The migration assay of BCC, BCC with overexpression of miR125b (treated with 50 nM of mimics of miR125b), wBCC, and wBCC with the inhibition of miR125b (treated with 25 nM of miR125b inhibitor), n = 3, *p < 0.05, **p < 0.01, ***p < 0.001. (J) The expression of miR-125b in WJ-EV and AT-EV, n = 3, **p < 0.01. (K) The expression of miR-125b in WJ-EV and WJ-EV-derived from WJ-MSC treated with 50 nM of miR-125b inhibitor (anti125b-WJ-EV), n = 3, **p < 0.01. (L) The expression of HIF1α in BCC, wBCC and BCC-internalized with anti125b-WJ-EV, n = 3, **p < 0.01. (M) The migration of BCC, wBCC and BCC-internalized with anti125b-WJ-EV, n = 3, *p < 0.05, **p < 0.01.