The role of MALAT1/miR-1/slug axis on radioresistance in nasopharyngeal carcinoma

Tumour Biol. 2016 Mar;37(3):4025-33. doi: 10.1007/s13277-015-4227-z. Epub 2015 Oct 20.

Abstract

Recent studies demonstrated that long non-coding RNAs (lncRNAs) have a critical role in the regulation of cancer progression and metastasis. However, little is known whether lncRNA regulated nasopharyngeal carcinoma (NPC) cell radioresistance. In the present study, we found that MALAT1 was significantly upregulated in NPC cell lines and tissues. Knockdown of MALAT1 could sensitize NPC cells to radiation both in vitro and in vivo. Interestingly, we found that MALAT1 regulated radioresistance by modulating cancer stem cell (CSC) activity. Furthermore, we found that there was reciprocal repression between MALAT1 and miR-1, and slug was identified as a downstream target of miR-1. Taking these observations into consideration, we proposed that MALAT1 regulated CSC activity and radioresistance by modulating miR-1/slug axis, which indicated that MALAT1 could act as a therapeutic target for NPC patients.

Keywords: MALAT1; Radioresistance; Slug; miR-1.

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Line, Tumor
  • Female
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mice, Nude
  • MicroRNAs / physiology*
  • Middle Aged
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / metabolism*
  • Nasopharyngeal Neoplasms / mortality
  • Nasopharyngeal Neoplasms / radiotherapy
  • Neoplasm Transplantation
  • RNA Interference
  • RNA, Long Noncoding / physiology*
  • Radiation Tolerance
  • Snail Family Transcription Factors / physiology*

Substances

  • MALAT1 long non-coding RNA, human
  • MIRN1 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • SNAI1 protein, human
  • Snail Family Transcription Factors