TDP-43 regulates cancer-associated microRNAs. Issue 10 (26th September 2017)

• Record Type: Journal Article
• Authors: Chen, Xiaowei; Fan, Zhen; McGee, Warren; Chen, Mengmeng; Kong, Ruirui; Wen, Pushuai; Xiao, Tengfei; Chen, Xiaomin; Liu, Jianghong; Zhu, Li; Chen, Runsheng; Wu, Jane Y
• Is Part Of: Protein & cell. Volume 9:Issue 10(2018)
• Page Start: 848
• Page End: 866
• Publication Date: 2017-09-26
• Subjects: TDP-43 -- miRNA -- cancer -- migration -- prognosis; Proteins -- Periodicals; Cells -- Periodicals; Cytology -- Periodicals; 572.6
• DOI: 10.1007/s13238-017-0480-9
• Languages: English
• ISSNs: 1674-800X

Abstract

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.