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Integrative analysis of mRNA-miRNA-TFs reveals the key regulatory connections involved in basal cell carcinoma

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Abstract

Basal cell carcinoma (BCC) is one of the most common skin cancers worldwide and contributes substantially to global morbidity, but its tumorigenesis and pathogenesis remain largely unknown. To investigate the crosstalk between microRNAs (miRNAs), mRNAs and transcription factors (TFs) and the regulatory processes underlying BCC, we have constructed an integrative miRNA-mRNA-TFs network based on RNA-sequencing datasets. In this study, two RNA-sequencing datasets and matched miRNA expression datasets of selected differentially-expressed genes (DEGs) were used to infer potential miRNA regulatory and TFs activities in BCC. A total of 1247 DEGs were identified by combining two BCC RNA-sequencing profiles. Furthermore, by integrating network interaction construction, we found 37 important dysregulated genes (ING3, VEGFA, TP63, MMP11, NRP1, HIF1A, APC, PTCH1, etc.) that are significantly associated with BCC, as well as a few novel potential miRNAs (miR-203, miR-29b, miR-141, miR-7b, miR-9, miR-200a, miR-7c and miR-132) and TFs (MYB, MYC, STAT3, ARNT, PAX5, CUX1, E2F1 and CEBPA). These identified potential genes and miRNA/TFs candidates may play direct/indirect roles in the molecular pathogenesis of BCC.

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Abbreviations

BCC:

Basal cell carcinoma

GEO:

Gene expression omnibus

PCA:

Principal component analysis

DGN:

DisGeNET v5.0

NCG:

Network of Cancer Genes 5.0

GO:

Gene Ontology

KEGG:

Kyoto Encyclopedia of Genes and Genomes

ING3:

Inhibitor of growth protein 3

PTCH1:

Protein patched homolog 1.

NRP1:

Neuropilin-1

TP63:

Transformation-related protein 63

MMP11:

Matrix metalloproteinase-11

HIF1A:

Hypoxia-inducible factor 1-alpha

APC:

Adenomatous polyposis coli

VEGFA:

Vascular endothelial growth factor A

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Acknowledgements

This study was funded by CW from National Natural Science Foundation of China (81860484).

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Author notes

  1. Chuan Wan and Yang Li contributed equally to this work and co-first authors.

Authors and Affiliations

  1. Department of Dermatology, The First Affiliated Hospital of Nanchang University, Nanchang, China

    Chuan Wan

  2. Department of Dermatology, The Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, China

    Yang Li

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  1. Chuan Wan
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  2. Yang Li
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Correspondence to Chuan Wan.

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Wan, C., Li, Y. Integrative analysis of mRNA-miRNA-TFs reveals the key regulatory connections involved in basal cell carcinoma. Arch Dermatol Res 312, 133–143 (2020). https://doi.org/10.1007/s00403-019-02002-y

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  • DOI: https://doi.org/10.1007/s00403-019-02002-y

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