SMARCA4 promotes benign skin malignant transformation into melanoma through Adherens junction signal transduction

Clin Transl Oncol. 2021 Mar;23(3):591-600. doi: 10.1007/s12094-020-02453-0. Epub 2020 Jul 27.

Abstract

Purpose: Melanoma is a malignant skin tumor, and its incidence is rising. To explore the specific differences in benign and malignant melanoma at the genetic level, we performed a series of bioinformatics analyses, including differential gene analysis, co-expression analysis, enrichment analysis, and regulatory prediction.

Methods: The microarray data of benign and malignant melanocytes were downloaded from GEO, and 1917 differential genes were obtained by differential analysis (p < 0.05). Weighted gene co-expression network analysis obtained three functional barrier modules. The essential genes of each module are SMARTA4, HECA, and C1R.

Results: The results of the enrichment analysis showed that the dysfunctional module gene was mainly associated with RNA splicing and Adherens junction. Through the pivotal analysis of ncRNA, it was found that miR-448, miR-152-3p, and miR-302b-3p essentially regulate three modules, which we consider to be critical regulators. In the pivot analysis of TF, more control modules include ARID3A, E2F1, E2F3, and E2F8.

Conclusions: We believe that the regulator (miR-448, miR-152-3p, miR-302b-3p) regulates the expression of the core gene SMARCA4, which in turn affects the signal transduction of the Adherens junction. It eventually leads to the deterioration of benign skin spasms into melanoma.

Keywords: Adherens junction; Melanoma; SMARCA4; WGCNA.

MeSH terms

  • Adherens Junctions / genetics*
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / pathology
  • Computational Biology
  • DNA Helicases / genetics*
  • DNA-Binding Proteins
  • Databases, Genetic
  • E2F1 Transcription Factor
  • E2F3 Transcription Factor
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks / genetics*
  • Humans
  • Melanocytes* / pathology
  • Melanoma / genetics*
  • Melanoma / pathology
  • Melanoma, Cutaneous Malignant
  • MicroRNAs
  • Neoplasm Proteins / genetics
  • Nuclear Proteins / genetics*
  • RNA Splicing / genetics
  • RNA, Messenger / genetics
  • RNA, Untranslated
  • Repressor Proteins
  • Signal Transduction
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • Tissue Array Analysis / methods
  • Transcription Factors / genetics*

Substances

  • ARID3A protein, human
  • DNA-Binding Proteins
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • E2F3 Transcription Factor
  • E2F3 protein, human
  • E2F8 protein, human
  • HECA protein, human
  • MIRN152 microRNA, human
  • MIRN302A microRNA, human
  • MIRN448 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • RNA, Untranslated
  • Repressor Proteins
  • Transcription Factors
  • SMARCA4 protein, human
  • DNA Helicases