Characterization and functional prediction of the microRNAs differentially expressed in a mouse model of concanavalin A-induced autoimmune hepatitis

被引:18
作者
Liu, Yang [1 ,2 ]
Chen, Hao [1 ,2 ]
Hao, Jianheng [1 ,2 ]
Li, Zhencheng [1 ,2 ]
Hou, Tiezheng [1 ,2 ]
Hao, Huiqin [1 ,2 ]
机构
[1] Shanxi Univ Chinese Med, Coll Basic Med Sci, Jinzhong 030619, Peoples R China
[2] Shanxi Univ Chinese Med, Basic Lab Integrated Tradit Chinese & Western Med, Jinzhong 030619, Peoples R China
关键词
autoimmune hepatitis; concanavalin A; microRNA; microarray; Gene Ontology; KEGG; KUPFFER CELLS; LIVER; BIOLOGY; FERROPTOSIS; MECHANISMS; TARGETS; TYPE-1; CANCER;
D O I
10.7150/ijms.47766
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In order to investigate the altered expression of microRNAs (miRNAs) in the development of autoimmune hepatitis (AIH), the aberrantly expressed miRNAs in the concanavalin A (Con A)-induced AIH mouse model were identified for the first time with microarray in this study. A total of 49 miRNAs (31 upand 18 down-regulated) were screened out, and the qRT-PCR validation results of 12 chosen miRNAs were consistent with the microarray data. Combined with the profiling of differently expressed mRNAs in the same model (data not shown), 959 predicted target genes (601 for upand 358 for down-regulated miRNAs) were obtained according to the intersection of databases miRWalk and miRDB, and several hub genes were obtained from the regulatory networks, including Cadm1 and Mier3. These target genes were significantly enriched in the Gene ontology (GO) terms of "transcription, DNA-templated", and were annotated in 47 signaling pathways, comprising "Wnt signaling pathway", "Hippo signaling pathway", "Ferroptosis" and "mitogen-activated protein kinase (MAPK) signaling pathway", according to the GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In the miRNA-GO-network, mmu-miR-193b-3p were exhibited in 33 GO terms of biological processes (BP), and the most significantly regulated GO term in BP categories was "regulation of transcription, DNA-templated". While in the miRNA-pathway-network, mmu-miR-7005-5p were enriched in 37 pathways, which was more than the other specifically expressed miRNAs, and the most significantly enriched pathways were "Endocytosis" and "MAPK signaling pathway". In conclusion, these differently expressed miRNAs seemed to be associated with the onset of AIH, and have the potential to serve as the new targets on the treatment of this disease.
引用
收藏
页码:2312 / 2327
页数:16
相关论文
共 68 条
[1]   Relation Between Immunohistochemical Expression of Hippo Pathway Effectors and Chronic Hepatitis Induced Fibrosis in Egyptian Patients [J].
Abdallah, Rania Abdallah ;
Shaban, Mohammad Ibrahim ;
Taie, Doha Maher ;
Asaad, Nancy Youssef ;
Badr, Aya Hamdy Abd El Bary .
TURKISH JOURNAL OF PATHOLOGY, 2020, 36 (01) :48-63
[2]   Cell Biology of T Cell Receptor Expression and Regulation [J].
Alcover, Andres ;
Alarcon, Balbino ;
Di Bartolo, Vincenzo .
ANNUAL REVIEW OF IMMUNOLOGY, VOL 36, 2018, 36 :103-125
[3]   Circulating microRNAs: Emerging Biomarkers of Liver Disease [J].
Arrese, Marco ;
Eguchi, Akiko ;
Feldstein, Ariel E. .
SEMINARS IN LIVER DISEASE, 2015, 35 (01) :43-54
[4]   MicroRNAs: Target Recognition and Regulatory Functions [J].
Bartel, David P. .
CELL, 2009, 136 (02) :215-233
[5]   The Gene Ontology Resource: 20 years and still GOing strong [J].
Carbon, S. ;
Douglass, E. ;
Dunn, N. ;
Good, B. ;
Harris, N. L. ;
Lewis, S. E. ;
Mungall, C. J. ;
Basu, S. ;
Chisholm, R. L. ;
Dodson, R. J. ;
Hartline, E. ;
Fey, P. ;
Thomas, P. D. ;
Albou, L. P. ;
Ebert, D. ;
Kesling, M. J. ;
Mi, H. ;
Muruganujian, A. ;
Huang, X. ;
Poudel, S. ;
Mushayahama, T. ;
Hu, J. C. ;
LaBonte, S. A. ;
Siegele, D. A. ;
Antonazzo, G. ;
Attrill, H. ;
Brown, N. H. ;
Fexova, S. ;
Garapati, P. ;
Jones, T. E. M. ;
Marygold, S. J. ;
Millburn, G. H. ;
Rey, A. J. ;
Trovisco, V. ;
dos Santos, G. ;
Emmert, D. B. ;
Falls, K. ;
Zhou, P. ;
Goodman, J. L. ;
Strelets, V. B. ;
Thurmond, J. ;
Courtot, M. ;
Osumi-Sutherland, D. ;
Parkinson, H. ;
Roncaglia, P. ;
Acencio, M. L. ;
Kuiper, M. ;
Laegreid, A. ;
Logie, C. ;
Lovering, R. C. .
NUCLEIC ACIDS RESEARCH, 2019, 47 (D1) :D330-D338
[6]   T cell receptor-based cancer immunotherapy: Emerging efficacy and pathways of resistance [J].
Chandran, Smita S. ;
Klebanoff, Christopher A. .
IMMUNOLOGICAL REVIEWS, 2019, 290 (01) :127-147
[7]   BMSCs-derived miR-223-containing exosomes contribute to liver protection in experimental autoimmune hepatitis [J].
Chen, Lu ;
Lu, Feng-bin ;
Chen, Da-zhi ;
Wu, Jin-lu ;
Hu, En-de ;
Xu, Lan-man ;
Zheng, Ming-hua ;
Li, Hui ;
Huang, Yu ;
Jin, Xiao-ya ;
Gong, Yue-wen ;
Lin, Zhuo ;
Wang, Xiao-dong ;
Chen, Yong-ping .
MOLECULAR IMMUNOLOGY, 2018, 93 :38-46
[8]   Wnt/β-Catenin Signaling and Disease [J].
Clevers, Hans ;
Nusse, Roel .
CELL, 2012, 149 (06) :1192-1205
[9]   Global Disparities and Their Implications in the Occurrence and Outcome of Autoimmune Hepatitis [J].
Czaja, Albert J. .
DIGESTIVE DISEASES AND SCIENCES, 2017, 62 (09) :2277-2292
[10]   Caveolin-1 dictates ferroptosis in the execution of acute immune-mediated hepatic damage by attenuating nitrogen stress [J].
Deng, Guanghui ;
Li, Yunjia ;
Ma, Shuoyi ;
Gao, Zhuowei ;
Zeng, Ting ;
Chen, Limei ;
Ye, Haixin ;
Yang, Menghan ;
Shi, Hao ;
Yao, Xiaofen ;
Zeng, Zhiyun ;
Chen, Yuyao ;
Song, Yuhong ;
Liu, Bing ;
Gao, Lei .
FREE RADICAL BIOLOGY AND MEDICINE, 2020, 148 :151-161