MicroRNA and transcriptome analysis in periocular Sebaceous Gland Carcinoma

Sci Rep. 2018 May 14;8(1):7531. doi: 10.1038/s41598-018-25900-z.

Abstract

Sebaceous gland carcinoma (SGC) is a rare, but life-threatening condition with a predilection for the periocular region. Eyelid SGC can be broadly categorised into two subtypes, namely either nodular or pagetoid with the latter being more aggressive and requiring radical excision to save life. We have identified key altered microRNAs (miRNA) involved in SGC shared by both subtypes, hsa-miR-34a-5p and hsa-miR-16-5p. However, their gene targets BCL2 and MYC were differentially expressed with both overexpressed in pagetoid but unchanged in nodular suggesting different modes of action of these two miRNAs on BCL/MYC expression. Hsa-miR-150p is nodular-specifically overexpressed, and its target ZEB1 was significantly downregulated in nodular SGC suggesting a tumour suppressor role. Invasive pagetoid subtype demonstrated specific overexpression of hsa-miR-205 and downregulation of hsa-miR-199a. Correspondingly, miRNA gene targets, EZH2 (by hsa-miR-205) and CD44 (by hsa-miR-199a), were both overexpressed in pagetoid SGC. CD44 has been identified as a potential cancer stem cell marker in head and neck squamous cell carcinoma and its overexpression in pagetoid cells represents a novel treatment target. Aberrant miRNAs and their gene targets have been identified in both SGC subtypes, paving the way for better molecular understanding of these tumours and identifying new treatment targets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Eyelid Neoplasms / genetics*
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks*
  • Humans
  • MicroRNAs / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-myc / genetics
  • Sebaceous Gland Neoplasms / genetics*
  • Zinc Finger E-box-Binding Homeobox 1 / genetics

Substances

  • BCL2 protein, human
  • MIRN150 microRNA, human
  • MIRN16 microRNA, human
  • MIRN205 microRNA, human
  • MIRN34 microRNA, human
  • MYC protein, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-myc
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1