Linc00423 as a tumor suppressor in retroperitoneal liposarcoma via activing MAPK signaling pathway through destabilizing of NFATC3

Cell Death Dis. 2019 Jun 3;10(6):430. doi: 10.1038/s41419-019-1658-2.

Abstract

Unraveling the noncoding RNA expression networks governing cancer initiation and development is essential while remains largely uncompleted in retroperitoneal liposarcoma (RLS). Through RNA-seq technologies and computational biology, deregulated long noncoding RNAs (lncRNAs) are being identified and reveal that lncRNAs are implicated in serial steps of RLS development. High-throughput sequencing with computational methods for assembling the transcriptome of five paired RLS patient's tissues. We found that long intergenic noncoding RNA 423 (linc00423) was downregulated in RLS tissues. Gain-of-function assays revealed that overexpressed linc00423 obviously inhibited RLS cell growth in vitro and in vivo. Additionally, RNA sequence, RNA-pulldown and RIP assays evidenced that linc00423 involved in MAPK signaling pathway via destabilizing of nuclear factor of activated T-cells 3 (NFATC3). Summing up, our findings demonstrated that linc00423 acted as the tumor suppressor in RLS cells through regulating the protein level of NFATC3 at a post-transcriptional level and negatively regulated the MAPK signaling pathway at a transcriptional level. Linc00423 might serve as a candidate prognostic biomarker and a target for novel therapies of RLS patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor*
  • HEK293 Cells
  • Humans
  • Liposarcoma / genetics
  • Liposarcoma / metabolism*
  • MAP Kinase Signaling System / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / metabolism*
  • Protein Binding
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA-Seq
  • Retroperitoneal Neoplasms / genetics
  • Retroperitoneal Neoplasms / metabolism*
  • Transplantation, Heterologous
  • Up-Regulation / genetics

Substances

  • CAHM long non-coding RNA, human
  • NFATC Transcription Factors
  • NFATC3 protein, human
  • RNA, Long Noncoding

Supplementary concepts

  • Retroperitoneal liposarcoma