TDP-43 regulates cancer-associated microRNAs

Xiaowei Chen, Zhen Fan, Warren McGee, Mengmeng Chen, Ruirui Kong, Pushuai Wen, Tengfei Xiao, Xiaomin Chen, Jianghong Liu, Li Zhu, Runsheng Chen*, Jane Y. Wu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Aberrant regulation of miRNA genes contributes to pathogenesis of a wide range of human diseases, including cancer. The TAR DNA binding protein 43 (TDP-43), a RNA/DNA binding protein associated with neurodegeneration, is involved in miRNA biogenesis. Here, we systematically examined miRNAs regulated by TDP-43 using RNA-Seq coupled with an siRNA-mediated knockdown approach. TDP-43 knockdown affected the expression of a number of miRNAs. In addition, TDP-43 down-regulation led to alterations in the patterns of different isoforms of miRNAs (isomiRs) and miRNA arm selection, suggesting a previously unknown role of TDP-43 in miRNA processing. A number of TDP-43 associated miRNAs, and their candidate target genes, are associated with human cancers. Our data reveal highly complex roles of TDP-43 in regulating different miRNAs and their target genes. Our results suggest that TDP-43 may promote migration of lung cancer cells by regulating miR-423-3p. In contrast, TDP-43 increases miR-500a-3p expression and binds to the mature miR-500a-3p sequence. Reduced expression of miR-500a-3p is associated with poor survival of lung cancer patients, suggesting that TDP-43 may have a suppressive role in cancer by regulating miR-500a-3p. Cancer-associated genes LIF and PAPPA are possible targets of miR-500a-3p. Our work suggests that TDP-43-regulated miRNAs may play multifaceted roles in the pathogenesis of cancer.

Original languageEnglish (US)
Pages (from-to)848-866
Number of pages19
JournalProtein and Cell
Volume9
Issue number10
DOIs
StatePublished - Oct 1 2018

Keywords

  • TDP-43
  • cancer
  • miRNA
  • migration
  • prognosis

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Drug Discovery
  • Cell Biology

Fingerprint Dive into the research topics of 'TDP-43 regulates cancer-associated microRNAs'. Together they form a unique fingerprint.

Cite this