SPLUNC1 regulates cell progression and apoptosis through the miR-141-PTEN/p27 pathway, but is hindered by LMP1

PLoS One. 2013;8(3):e56929. doi: 10.1371/journal.pone.0056929. Epub 2013 Mar 5.

Abstract

Little is known about the role of the host defensive protein short palate, lung and nasal epithelium clone 1 (SPLUNC1) in the carcinogenesis of nasopharyngeal carcinoma (NPC). Here we report that SPLUNC1 plays a role at a very early stage of NPC carcinogenesis. SPLUNC1 regulates NPC cell proliferation, differentiation and apoptosis through miR-141, which in turn regulates PTEN and p27 expression. This signaling axis is negatively regulated by the EBV-coded gene LMP1. Therefore we propose that SPLUNC1 suppresses NPC tumor formation and its inhibition by LMP1 provides a route for NPC tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Carcinoma
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Proliferation
  • Coculture Techniques
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Gene Expression Regulation, Neoplastic
  • Glycoproteins / metabolism*
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / metabolism
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / metabolism*
  • PTEN Phosphohydrolase / metabolism
  • Phosphoproteins / metabolism*
  • Signal Transduction*
  • Viral Matrix Proteins / metabolism*

Substances

  • BPIFA1 protein, human
  • CDKN1B protein, human
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Glycoproteins
  • MIRN141 microRNA, human
  • MicroRNAs
  • Phosphoproteins
  • Viral Matrix Proteins
  • Green Fluorescent Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • PTEN Phosphohydrolase
  • PTEN protein, human

Grants and funding

This study was supported by grants from the National High Technology Research and Development Program of China (2012AA02A206), the National Natural Science Foundation of China (91229122, 81071644, 81101509, 81171934, 81172189, 81171930, 81272298, 81272254 and 30971147), the 111 Project (111-2-12) and the Hunan Province Natural Sciences Foundation of China (10JJ7003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.