Open AccessTDP-43 regulates cancer-associated microRNAs
Author(s) -
Xiaowei Chen,
Zhen Fan,
W Ambrose McGee,
Mengmeng Chen,
Ruirui Kong,
Pushuai Wen,
Tengfei Xiao,
Xiaomin Chen,
Jianghong Liu,
Li Zhu,
Runsheng Chen,
Jane Y. Wu
Publication year - 2017
Publication title -
protein and cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.973
H-Index - 63
eISSN - 1674-8018
pISSN - 1674-800X
DOI - 10.1007/s13238-017-0480-9
Subject(s) - microrna , gene knockdown , biology , drosha , gene , cancer research , cancer , gene expression , regulation of gene expression , gene isoform , genetics , rna , rna interference
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. Electronic supplementary material The online version of this article (doi:10.1007/s13238-017-0480-9) contains supplementary material, which is available to authorized users.