Identification of unique microRNA signature associated with lupus nephritis.
MicroRNAs (miRNA) have emerged as an important new class of modulators of gene expression. In this study we investigated miRNA that are differentially expressed in lupus nephritis. Microarray technology was used to investigate differentially expressed miRNA in peripheral blood mononuclear cells (PBMCs) and Epstein-Barr Virus (EBV)-transformed cell lines obtained from lupus nephritis affected patients and unaffected controls. TaqMan-based stem-loop real-time polymerase chain reaction was used for validation. Microarray analysis of miRNA expressed in both African American (AA) and European American (EA) derived lupus nephritis samples revealed 29 and 50 differentially expressed miRNA, respectively, of 850 tested. There were 18 miRNA that were differentially expressed in both racial groups. When samples from both racial groups and different specimen types were considered, there were 5 primary miRNA that were differentially expressed. We have identified 5 miRNA; hsa-miR-371-5P, hsa-miR-423-5P, hsa-miR-638, hsa-miR-1224-3P and hsa-miR-663 that were differentially expressed in lupus nephritis across different racial groups and all specimen types tested. Hsa-miR-371-5P, hsa-miR-1224-3P and hsa-miR-423-5P, are reported here for the first time to be associated with lupus nephritis. Our work establishes EBV-transformed B cell lines as a useful model for the discovery of miRNA as biomarkers for SLE. Based on these findings, we postulate that these differentially expressed miRNA may be potential novel biomarkers for SLE as well as help elucidate pathogenic mechanisms of lupus nephritis. The investigation of miRNA profiles in SLE may lead to the discovery and development of novel methods to diagnosis, treat and prevent SLE.
Te
Jeannie L
JL
Department of Arthritis and Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America.
Dozmorov
Igor M
IM
Guthridge
Joel M
JM
Nguyen
Kim L
KL
Cavett
Joshua W
JW
Kelly
Jennifer A
JA
Bruner
Gail R
GR
Harley
John B
JB
Ojwang
Joshua O
JO
D001741:Black or African American / Q000235:genetics; D001402:B-Lymphocytes / Q000378:metabolism; D002461:Cell Line, Transformed; D005060:Europe; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D008181:Lupus Nephritis / Q000208:ethnology / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results; D014430:Twins, Monozygotic / Q000235:genetics
D035683:MicroRNAs