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MicroRNAs Associated with Keloids Identified by Microarray Analysis and In Vitro Experiments

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Abstract

MicroRNAs (miRNAs) play a crucial role in gene regulation and the development of keloid. This research aimed to identify and verify miRNAs associated with keloids by microarray analysis and in vitro experiments, shedding light on seeking for potential therapeutic molecular targets. In this study, the weighted gene co-expression network analysis was performed based on the GSE113620. The key miRNA module most relevant to the keloid was further screened to identify hub miRNAs, and then hub miRNAs was verified by the microarray analysis and qRT-PCR experiments. Additionally, targeted genes of hub miRNAs were predicted and verified. Gene ontology (GO) analysis and KEGG enrichment analysis were also conducted. Five miRNA modules were divided, and the blue module exhibited the highest correlation with keloids. Then, hsa-miR-127-3p, hsa-miR-214-3p, hsa-miR-155-5p, hsa-miR-409-5p, and hsa-miR-542-5p were identified as the hub miRNAs. Subsequently, the microarray analysis and qRT-PCR results demonstrated that the expression of five miRNAs were upregulated in keloid tissues. The GO analysis revealed that the target genes of these miRNAs were mainly enriched in biological processes including gene transcription, protein phosphorylation and the MAPK (mitogen-activated protein kinase) cascade, and the KEGG pathway enrichment analysis showed that the PI3K-AKT signaling pathway were significantly enriched. In conclusion, these five miRNAs (hsa-miR-127-3p, hsa-miR-155-5p, hsa-miR-214-3p, hsa-miR-409-5p, and hsa-miR-542-5p) play vital roles in the pathogenesis of keloid and might be potential therapeutic targets. These miRNAs might regulate genes enriched in gene transcription, protein phosphorylation, the MAPK cascade, and the PI3K-Akt signaling pathway.

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Data Availability

The dataset described in this article can be freely and openly accessed at the GEO database (https://www.ncbi.nlm.nih.gov/geo/).

Abbreviations

GEO:

Gene expression omnibus

WGCNA:

Weighted gene co-expression network analysis

qRT-PCR:

Quantitative reverse transcription polymerase chain reaction

STRING:

Search tool for the retrieval of interacting genes/proteins database

GO:

Gene ontology

KEGG:

Kyoto encyclopedia of genes and genomes

3’-UTR:

3'-untranslated region

TGF-β:

Transforming growth factor-β

TOM:

Topological overlap matrix

ME:

Module eigengenes

MS:

Module significance

MM:

Module membership

GS:

Gene significance

STRING:

Search Tool for the Retrieval of Interacting Genes/Proteins

PPI:

Protein–protein interaction

BP:

Biological process

CC:

Cellular component

MF:

Molecular function

MAPK:

Mitogen-activated protein kinase

PI3K/Akt:

Phosphatidylinositol-3-kinase/protein-serine-threonine

EMT:

Epithelial–mesenchymal transition

ERKs:

Extracellular signal-regulated kinases

JNK:

Jun NH2-terminal kinase

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Acknowledgements

None.

Funding

This work was supported by National Natural Science Foundation of China (81971846) and National High Level Hospital Clinical Research Funding (Grant nos. 2022-PUMCH-B-042, 2022-PUMCH-B-041, 2022-PUMCH-A-210 and 2022-PUMCH-C-025).

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Authors and Affiliations

  1. Department of Plastic and Reconstructive Surgery, Peking Union Medical college Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Sichao Chen, Wenchao Zhang, Zenan Xia, Jiangmiao Xie, Zhijin Li, Nanze Yu & Xiaojun Wang

  2. Department of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Zeming Liu

  3. Department of International Medical Service, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Nanze Yu

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Contributions

Conceptualization, methodology, and resources: SC and ZML; Investigation, data curation, formal analysis, validation, software, project administration, and supervision: WZ, ZX, JX, and ZZL; Writing and visualization: SC; and Funding acquisition: NY and XW. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Nanze Yu or Xiaojun Wang.

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The written informed consent was obtained from all the patients and the study protocol was approved by the Bioethical Committee of Peking Union Medical College Hospital (ZS-2222).

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Chen, S., Zhang, W., Xia, Z. et al. MicroRNAs Associated with Keloids Identified by Microarray Analysis and In Vitro Experiments. Mol Biotechnol (2024). https://doi.org/10.1007/s12033-024-01058-0

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