The biological function and diagnostic value of miR-762 in nasopharyngeal carcinoma

Liu

et al. 2022

J Nanobiotechnol

Background The use of keratinocytes derived from induced pluripotent stem cells (iPSCs-KCs) may represent a novel cell therapy strategy for burn treatment. There is growing evidence that extracellular vesicles, including exosomes, are primary mediators of the benefits of stem cell therapy. Herein, we thus explored the effects of exosomes produced by iPSCs-derived keratinocytes (iPSCs-KCs-Exos) in a model of deep second-degree burn wound healing and evaluated the mechanistic basis for the observed activity. Methods iPSCs-KCs-Exos were isolated from conditioned medium of iPSCs-KCs and verified by electron micrograph and size distribution. Next, iPSCs-KCs-Exos were injected subcutaneously around wound sites, and its efficacy was evaluated by measuring wound closure areas, histological examination, and immunohistochemistry staining. The effects of iPSCs-KCs-Exos on proliferation and migration of keratinocytes and endothelial cells in vitro were assessed by EdU staining, wound healing assays, and transwell assay. Then, high-throughput microRNA sequencing was used to explore the underlying mechanisms. We assessed the roles of miR-762 in iPSCs-KCs-Exos-induced regulation of keratinocytes and endothelial cells migration. Furthermore, the target gene which mediated the biological effects of miR-762 in keratinocytes and endothelial cells was also been detected. Results The analysis revealed that iPSCs-KCs-Exos application to the burn wound drove the acceleration of wound closure, with more robust angiogenesis and re-epithelialization being evident. Such iPSCs-KCs-Exos treatment effectively enhanced endothelial cell and keratinocyte migration in vitro. Moreover, the enrichment of miR-762 was detected in iPSCs-KCs-Exos and was found to target promyelocytic leukemia (PML) as a means of regulating cell migration through a mechanism tie to integrin beta1 (ITGB1). Conclusion These results thus provide a foundation for the further study of iPSCs-KCs-Exos as novel cell-free treatments for deep second-degree burns. Graphical Abstract

Section: Discussionmentioning

confidence: 99%

Exosomes from human induced pluripotent stem cells-derived keratinocytes accelerate burn wound healing through miR-762 mediated promotion of keratinocytes and endothelial cells migration

Liu

et al. 2022

J Nanobiotechnol

“…However, the role of miR‐762 has been explored in various cancers. In nasopharyngeal carcinoma, upregulation of miR‐762 was suggested to associate with progression by promoting tumor cells' proliferation and invasion 22 . The miR‐762 has been reported to involve in the circRNA‐miRNA‐mRNA network in lung cancer as diagnostic or prognostic factor 23,24 .…”

Section: Discussionmentioning

confidence: 99%

“…In nasopharyngeal carcinoma, upregulation of miR-762 was suggested to associate with progression by promoting tumor cells' proliferation and invasion. 22 The miR-762 has been reported to involve in the circRNA-miRNA-mRNA network in lung cancer as diagnostic or prognostic factor. 23,24 Although the underlying links between SLE/NPSLE and various cancers remain unclear, it's no doubt that immune dysfunction is the common ground of these diseases.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of microRNA‐762 suppresses the expression of GIPC3 in systemic lupus erythematosus and neuropsychiatric systemic lupus erythematosus

Immunity Inflam & Disease

Chi

et al. 2022

Background Systemic lupus erythematosus (SLE), especially neuropsychiatric SLE (NPSLE), is a complex systemic autoimmune disease, characterized by variable course and multiple organ dysfunction. Our study aimed to identify crucial microRNA (miRNAs) in SLE and NPSLE. Methods Totally 12 cases of serum specimens were collected from General Hospital of Ningxia Medical University (SLE = 4, NPSLE = 4, control = 4). After miRNA sequencing, differential expression analysis, miRNA target prediction, and miRNA‐messenger RNA (mRNA) regulatory network construction were performed to identify the hub miRNAs. The expression of target gene was determined by quantitative reverse transcription‐polymerase chain reaction and Western blot. Results There were 79 and 59 differentially expressed miRNAs (DEmiRNAs) in NPSLE versus Control, and SLE versus Control, respectively. Among 35 overlapped DEmiRNAs, 5 upregulated miRNAs' (hsa‐miR‐762, hsa‐miR‐4270, hsa‐miR‐3663‐3p, hsa‐miR‐4778‐5p, and hsa‐miR‐4516) target genes were supported by at least six databases. The miRNA‐mRNA network indicated that core miRNA hsa‐miR‐762 regulated 1270 target genes. MiR‐762 was significantly upregulated in SLE and NPSLE, and over expression of miR‐762 significantly suppressed GIPC PDZ domain containing family member 3 (GIPC3) expression in SLE and NPSLE. Conclusions Upregulation of hub miRNA miR‐762 can suppress the expression of GIPC3 in both SLE and NPSLE samples, which is probably involved in the development of SLE and NPSLE. Meanwhile, along with the development from SLE to NPSLE, miR‐762 exhibits higher expression.

“…In prior research, miR-762 has been found to regulate a range of target genes in different contexts. The upregulation of miR-762 in non-small cell lung cancer, bladder cancer, breast cancer and nasopharyngeal carcinoma has been linked to enhanced tumor cell invasivity, migration, and proliferation [30][31][32][33]. However, there have been no prior studies regarding the role of this speci c miRNA in keratinocytes or endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Exosomes From Human Induced Pluripotent Stem Cells-derived Keratinocytes Accelerate Burn Wound Healing Through miR-762 Mediated Promotion of Keratinocytes and Endothelial Cells Migration

Liu

et al. 2022

Preprint

Background: The use of keratinocytes derived from induced pluripotent stem cells (iPSCs-KCs) may represent a novel cell therapy strategy for burn treatment. There is growing evidence that extracellular vesicles, including exosomes, are primary mediators of the benefits of stem cell therapy. Herein, we thus explored the effects of exosomes produced by iPSCs-derived keratinocytes (iPSCs-KCs-Exos) in a model of deep second-degree burn wound healing and evaluated the mechanistic basis for the observed activity. Methods: iPSCs-KCs-Exos were isolated from conditioned medium of iPSCs-KCs and verified by electron micrograph and size distribution. Next, iPSCs-KCs-Exos were injected subcutaneously around wound sites, and its efficacy was evaluated by measuring wound closure areas, histological examination and immunohistochemistry staining. The effects of iPSCs-KCs-Exos on proliferation and migration of keratinocytes and endothelial cells in vitro were assessed by EdU staining, wound healing assays and transwell assay. Then, high-throughput microRNA sequencing was used to explore the underlying mechanisms. We assessed the roles of miR-762 in iPSCs-KCs-Exos-induced regulation of keratinocytes and endothelial cells migration. Furthermore, the target gene which mediated the biological effects of miR-762 in keratinocytes and endothelial cells was also been detected. Results: The analysis revealed that iPSCs-KCs-Exos application to the burn wound drove the acceleration of wound closure, with more robust angiogenesis and re-epithelialization being evident. Such iPSCs-KCs-Exos treatment effectively enhanced endothelial cell and keratinocyte migration in vitro. Moreover, the enrichment of miR-762 was detected in iPSCs-KCs-Exos and was found to target promyelocytic leukemia (PML) as a means of regulating cell migration through a mechanism tie to integrin beta1 (ITGB1). Conclusion: These results thus provide a foundation for the further study of iPSCs-KCs-Exos as novel cell-free treatments for deep second-degree burns.