Contributions
Abstract: P430
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Genetics/Epigenetics
MicroRNAs (miRs) play an important role in regulating gene expression by degrading transcripts and/or repressing translation. The miR-548ac-encoding sequence is located in the CD58 gene locus. Genetic variants in this locus have been linked to an increased risk of multiple sclerosis (MS) and also to different expression levels of miR-548ac. This molecule may play a causal role in MS pathogenesis.
The specific function of miR-548ac has not been investigated before. We aimed at identifying the target genes of this miR to enhance the understanding of the contribution of this molecule to the development of MS.
HeLa cells were transfected with mir-548ac precursor-encoding plasmids to overexpress mature miR-548ac. With real-time PCR assays, the levels of mature miR-548ac were measured 24 h and 48 h post transfection. Transcriptome profiling analysis was used to identify significantly downregulated transcripts. The most likely direct targets of miR-548ac were verified bioinformatically and experimentally validated with luciferase reporter assays.
In response to overexpression of miR-548ac, 257 (24 h) and 99 (48 h) transcripts were found to be significantly downregulated. Bioinformatically, ten were determined to be the most likely direct targets of miR-548ac, including the transcripts of SDC4, SEL1L and TNFAIP3. Luciferase assays confirmed a direct interaction of miR-548ac with the 3'ends of these molecules, which have been associated with immunomodulatory processes before.
To conclude, our findings imply that miR-548ac modulates immunological mechanisms. Other miRs map to genetic MS susceptibility loci as well. Investigating their functional roles will provide further insights into the molecular mechanisms underlying MS. Such efforts might also be of relevance for the identification of novel biomarkers for the disease.
Disclosure: NB received travel funds from Novartis. MH received speaking fees and travel funds from Bayer HealthCare, Biogen, Novartis and Teva. UKZ received speaking fees and financial support for research activities from Almirall, Bayer HealthCare, Biogen, Merck Serono, Novartis, Sanofi Genzyme and Teva. BF and DK declare no conflicts of interest.
Abstract: P430
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Genetics/Epigenetics
MicroRNAs (miRs) play an important role in regulating gene expression by degrading transcripts and/or repressing translation. The miR-548ac-encoding sequence is located in the CD58 gene locus. Genetic variants in this locus have been linked to an increased risk of multiple sclerosis (MS) and also to different expression levels of miR-548ac. This molecule may play a causal role in MS pathogenesis.
The specific function of miR-548ac has not been investigated before. We aimed at identifying the target genes of this miR to enhance the understanding of the contribution of this molecule to the development of MS.
HeLa cells were transfected with mir-548ac precursor-encoding plasmids to overexpress mature miR-548ac. With real-time PCR assays, the levels of mature miR-548ac were measured 24 h and 48 h post transfection. Transcriptome profiling analysis was used to identify significantly downregulated transcripts. The most likely direct targets of miR-548ac were verified bioinformatically and experimentally validated with luciferase reporter assays.
In response to overexpression of miR-548ac, 257 (24 h) and 99 (48 h) transcripts were found to be significantly downregulated. Bioinformatically, ten were determined to be the most likely direct targets of miR-548ac, including the transcripts of SDC4, SEL1L and TNFAIP3. Luciferase assays confirmed a direct interaction of miR-548ac with the 3'ends of these molecules, which have been associated with immunomodulatory processes before.
To conclude, our findings imply that miR-548ac modulates immunological mechanisms. Other miRs map to genetic MS susceptibility loci as well. Investigating their functional roles will provide further insights into the molecular mechanisms underlying MS. Such efforts might also be of relevance for the identification of novel biomarkers for the disease.
Disclosure: NB received travel funds from Novartis. MH received speaking fees and travel funds from Bayer HealthCare, Biogen, Novartis and Teva. UKZ received speaking fees and financial support for research activities from Almirall, Bayer HealthCare, Biogen, Merck Serono, Novartis, Sanofi Genzyme and Teva. BF and DK declare no conflicts of interest.