miR-1, regulated by LMP1, suppresses tumour growth and metastasis by targeting K-ras in nasopharyngeal carcinoma

Int J Exp Pathol. 2015 Dec;96(6):427-32. doi: 10.1111/iep.12162. Epub 2016 Jan 19.

Abstract

There is evidence to show that downregulation of miR-1 expression is closely related to cancer progression, including in nasopharyngeal carcinoma (NPC). However, the molecular mechanisms underlying miR-1 downregulation in NPC remain largely unknown, especially its association with Epstein-Barr virus (EBV). In this study we found that restoration of miR-1 dramatically inhibited cell invasion in vitro, together with tumour growth and metastasis in vivo. Importantly, we found that LMP1, an Epstein-Barr virus (EBV)-associated protein, suppressed miR-1 expression. Furthermore, we identified K-ras as a novel direct target of miR-1. Our results demonstrated for the first time that miR-1 was suppressed by LMP1 and its tumour-suppressive effects were mediated chiefly by repressing K-ras expression. We propose that miR-1 could serve as an independent biomarker to identify patients with different clinical characteristics.

Keywords: EBV; K-ras; LMP1; miR-1; nasopharyngeal carcinoma.

MeSH terms

  • Animals
  • Carcinoma / genetics
  • Carcinoma / metabolism*
  • Carcinoma / secondary
  • Carcinoma / virology
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / metabolism*
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / virology
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Proto-Oncogene Proteins p21(ras) / metabolism*
  • RNA, Small Interfering
  • RNAi Therapeutics
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction
  • Time Factors
  • Transfection
  • Tumor Burden
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • EBV-associated membrane antigen, Epstein-Barr virus
  • KRAS protein, human
  • MIRN1 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Viral Matrix Proteins
  • Proto-Oncogene Proteins p21(ras)