LncRNA MT1JP functions as a tumor suppressor by interacting with TIAR to modulate the p53 pathway

Oncotarget. 2016 Mar 29;7(13):15787-800. doi: 10.18632/oncotarget.7487.

Abstract

Accumulating evidence suggests that long noncoding RNAs (lncRNAs) play important roles in transcriptional regulation, whereas the extent to which the lncRNAs also function at the posttranscriptional level is less known. In the present study, we report a lncRNA named MT1JP which acts as a tumor suppressor through a posttranscriptional mechanism. We found that MT1JP is differentially expressed in tumor tissues by analyzing data from a customized microarray applied to 76 pairs of matched normal and cancer tissue samples. By associating with the RNA-binding protein TIAR, MT1JP enhanced the translation of the master transcription factor p53, thereby regulating a series of pathways involving p53, such as the cell cycle, apoptosis and proliferation. When MT1JP was down-regulated, the protein level of p53 declined, which in turn accelerated cell deterioration and tumor formation. Moreover, differential expression of MT1JP in cancerous and normal tissues suggests that it may be a promising prognostic marker and a therapeutic target. Taken together, we identified MT1JP as a critical factor in restraining cell transformation by modulating p53 translation through interactions with TIAR, and this finding is likely to shed new light on future investigations about posttranscriptional or translational effects of lncRNAs during cell transformation.

Keywords: MT1JP; TIAR; long noncoding RNAs; p53; tumor suppressor.

MeSH terms

  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / genetics*
  • Gene Expression Regulation, Neoplastic / genetics*
  • Genes, Tumor Suppressor
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • RNA, Long Noncoding / genetics*
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Signal Transduction / physiology
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • Tumor Suppressor Protein p53
  • TIAL1 protein, human