P2RX7-V3 is a novel oncogene that promotes tumorigenesis in uveal melanoma

Tumour Biol. 2016 Oct;37(10):13533-13543. doi: 10.1007/s13277-016-5141-8. Epub 2016 Jul 28.

Abstract

Uveal melanoma (UM) has a high mortality rate for primary intraocular tumors. Approximately half of UM patients present with untreatable and fatal metastases. Long non-coding RNAs (lncRNAs) have emerged as potent regulatory RNAs that play key roles in various cellular processes and tumorigenesis. However, to date, their roles in UM are not well-known. Here, we identified a transcriptional variant transcribed from the P2RX7 gene locus, named P2RX7-V3 (P2RX7 variant 3), which was expressed at a high level in UM cells. P2RX7-V3 silencing revealed that this variant acts as a necessary UM oncoRNA. Knockdown of P2RX7-V3 expression significantly suppressed tumor growth in vitro and in vivo. A genome-wide cDNA array revealed that a variety of genes were dysregulated following P2RX7-V3 silencing. These observations identified P2RX7-V3 that plays a crucial role in UM tumorigenesis and may serve as a useful biomarker in the diagnosis and prognosis treatment of UM in the future.

Keywords: Metastasis; P2RX7; Uveal melanoma; Variant; lncRNA; oncoRNA.

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics*
  • Blotting, Western
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Profiling
  • Humans
  • Immunoenzyme Techniques
  • Melanoma / genetics
  • Melanoma / metabolism
  • Melanoma / pathology*
  • Mice
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Receptors, Purinergic P2X7 / genetics
  • Receptors, Purinergic P2X7 / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • Uveal Neoplasms / genetics
  • Uveal Neoplasms / metabolism
  • Uveal Neoplasms / pathology*
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • P2RX7 protein, human
  • RNA, Messenger
  • Receptors, Purinergic P2X7

Supplementary concepts

  • Uveal melanoma