Transcriptomic identification of miR-205 target genes potentially involved in metastasis and survival of cutaneous malignant melanoma

Sci Rep. 2020 Mar 16;10(1):4771. doi: 10.1038/s41598-020-61637-4.

Abstract

Cutaneous melanoma is an aggressive neoplasm and is responsible for the majority of skin cancer deaths. Several miRNAs are involved in melanoma tumor progression. One of them is miR-205, the loss of which contributes to the development of melanoma metastasis. We evaluated whole-genome mRNA expression profiling associated with different miR-205 expression levels in melanoma cells. Differential expression analysis identified 243 differentially expressed transcripts including inositol polyphosphate 5'-phosphatase-like protein-1 (INPPL1) and BTB/POZ Domain-Containing Protein 3 (BTBD3). INPPL1 and BTBD3 were downregulated when melanoma cells expressed miR-205, indicating that these genes are potential miR-205 targets. Additionally, the target prediction algorithm TargetScan revealed that INPPL1 and BTBD3 genes had predicted target sites of miR-205 in their 3'UTRs and functional analysis demonstrated that these genes were directly linked to miR-205. Interestingly, our clinical data showed that INPPL1 was significantly associated with lymph node metastasis-free survival (LNMFS), distant metastasis-free survival (DMFS) and melanoma specific survival (MSS). This study supports INPPL1 as a miR-205 target gene and, therefore, that the involvement of miR-205 in the metastatic dissemination of malignant melanoma is, at least in part, via INPPL1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Disease-Free Survival
  • Down-Regulation / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Lymphatic Metastasis / genetics*
  • Melanoma / genetics*
  • Melanoma / mortality
  • Melanoma / pathology*
  • MicroRNAs / genetics*
  • MicroRNAs / physiology*
  • Neoplasm Metastasis / genetics*
  • Nerve Tissue Proteins / economics*
  • Nerve Tissue Proteins / genetics
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases / genetics*
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology*
  • Transcriptome / genetics*
  • Tumor Cells, Cultured

Substances

  • 3' Untranslated Regions
  • BTBD3 protein, human
  • MIRN205 microRNA, human
  • MicroRNAs
  • Nerve Tissue Proteins
  • INPPL1 protein, human
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases