TDP-43 regulates cancer-associated microRNAs.
10.1007/s13238-017-0480-9
- Author:
Xiaowei CHEN
1
;
Zhen FAN
1
;
Warren MCGEE
2
;
Mengmeng CHEN
3
;
Ruirui KONG
3
;
Pushuai WEN
3
;
Tengfei XIAO
1
;
Xiaomin CHEN
1
;
Jianghong LIU
3
;
Li ZHU
3
;
Runsheng CHEN
4
;
Jane Y WU
5
Author Information
1. CAS Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
2. Department of Neurology, Center for Genetic Medicine, Lurie Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
3. State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
4. CAS Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. rschen@ibp.ac.cn.
5. State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. jane-wu@northwestern.edu.
- Publication Type:Journal Article
- Keywords:
TDP-43;
cancer;
miRNA;
migration;
prognosis
- MeSH:
Animals;
Cells, Cultured;
DNA-Binding Proteins;
metabolism;
Electrophoretic Mobility Shift Assay;
Humans;
Immunoprecipitation;
Mice;
MicroRNAs;
genetics;
metabolism;
Neoplasms;
genetics;
metabolism
- From:
Protein & Cell
2018;9(10):848-866
- CountryChina
- Language:English
-
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.
