Global circRNA expression changes predate clinical and histological improvements of psoriasis patients upon secukinumab treatment.
Psoriasis is a common chronic inflammatory skin disease accompanied by heterogenous clinical and histological features, including a characteristic keratinocyte hyperproliferation and dermal immunogenic profile. In addition, psoriasis is associated with widespread transcriptomic alterations including...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0275219 |
| _version_ | 1811195552841334784 |
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| author | Sabine Seeler Liviu-Ionut Moldovan Trine Bertelsen Henrik Hager Lars Iversen Claus Johansen Jørgen Kjems Lasse Sommer Kristensen |
| author_facet | Sabine Seeler Liviu-Ionut Moldovan Trine Bertelsen Henrik Hager Lars Iversen Claus Johansen Jørgen Kjems Lasse Sommer Kristensen |
| author_sort | Sabine Seeler |
| collection | DOAJ |
| description | Psoriasis is a common chronic inflammatory skin disease accompanied by heterogenous clinical and histological features, including a characteristic keratinocyte hyperproliferation and dermal immunogenic profile. In addition, psoriasis is associated with widespread transcriptomic alterations including changes in microRNA (miRNA) and circular RNA (circRNA) abundance, which constitute non-coding RNA (ncRNA) classes with specific regulatory capacities in diverse physiological and pathological processes. However, the knowledge about the expression dynamics of ncRNA during psoriasis treatment is sparse. To elucidate the dynamics of miRNA and circRNA abundance during secukinumab (anti-IL-17A) treatment, we studied their expression patterns in skin biopsies from 14 patients with severe plaque-type psoriasis before and during an 84-day secukinumab therapy at day 0, 4, 14, 42, and 84 using NanoString nCounter technology. We found a comprehensive downregulation of the majority of investigated circRNAs and specific alterations in the miRNA profile, including an upregulation of miR-203a-3p, miR-93-5p, and miR-378i in lesional compared to non-lesional skin before treatment. During treatment, the circRNAs progressively returned to the expression levels observed in non-lesional skin and already four days after treatment initiation most circRNAs were significantly upregulated. In comparison, for miRNAs, the normalization to baseline during treatment was delayed and limited to a subset of miRNAs. Moreover, we observed a strong correlation between multiple circRNAs, including ciRS-7 and circPTPRA, and the psoriasis area and severity index (PASI). Similar pronounced correlations could, however, not be found for miRNAs. Finally, we did not observe any significant changes in circRNA expression in peripheral blood mononuclear cells during treatment. In conclusion, we uncovered a rapid shift in global circRNA abundance upon anti-IL-17A treatment, which predated clinical and histological improvements, and a strong correlation with PASI, indicating a biomarker potential of individual circRNAs. |
| first_indexed | 2024-04-12T00:45:02Z |
| format | Article |
| id | doaj.art-8509030fd17848ec958f7cae86d00585 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T00:45:02Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-8509030fd17848ec958f7cae86d005852022-12-22T03:54:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01179e027521910.1371/journal.pone.0275219Global circRNA expression changes predate clinical and histological improvements of psoriasis patients upon secukinumab treatment.Sabine SeelerLiviu-Ionut MoldovanTrine BertelsenHenrik HagerLars IversenClaus JohansenJørgen KjemsLasse Sommer KristensenPsoriasis is a common chronic inflammatory skin disease accompanied by heterogenous clinical and histological features, including a characteristic keratinocyte hyperproliferation and dermal immunogenic profile. In addition, psoriasis is associated with widespread transcriptomic alterations including changes in microRNA (miRNA) and circular RNA (circRNA) abundance, which constitute non-coding RNA (ncRNA) classes with specific regulatory capacities in diverse physiological and pathological processes. However, the knowledge about the expression dynamics of ncRNA during psoriasis treatment is sparse. To elucidate the dynamics of miRNA and circRNA abundance during secukinumab (anti-IL-17A) treatment, we studied their expression patterns in skin biopsies from 14 patients with severe plaque-type psoriasis before and during an 84-day secukinumab therapy at day 0, 4, 14, 42, and 84 using NanoString nCounter technology. We found a comprehensive downregulation of the majority of investigated circRNAs and specific alterations in the miRNA profile, including an upregulation of miR-203a-3p, miR-93-5p, and miR-378i in lesional compared to non-lesional skin before treatment. During treatment, the circRNAs progressively returned to the expression levels observed in non-lesional skin and already four days after treatment initiation most circRNAs were significantly upregulated. In comparison, for miRNAs, the normalization to baseline during treatment was delayed and limited to a subset of miRNAs. Moreover, we observed a strong correlation between multiple circRNAs, including ciRS-7 and circPTPRA, and the psoriasis area and severity index (PASI). Similar pronounced correlations could, however, not be found for miRNAs. Finally, we did not observe any significant changes in circRNA expression in peripheral blood mononuclear cells during treatment. In conclusion, we uncovered a rapid shift in global circRNA abundance upon anti-IL-17A treatment, which predated clinical and histological improvements, and a strong correlation with PASI, indicating a biomarker potential of individual circRNAs.https://doi.org/10.1371/journal.pone.0275219 |
| spellingShingle | Sabine Seeler Liviu-Ionut Moldovan Trine Bertelsen Henrik Hager Lars Iversen Claus Johansen Jørgen Kjems Lasse Sommer Kristensen Global circRNA expression changes predate clinical and histological improvements of psoriasis patients upon secukinumab treatment. PLoS ONE |
| title | Global circRNA expression changes predate clinical and histological improvements of psoriasis patients upon secukinumab treatment. |
| title_full | Global circRNA expression changes predate clinical and histological improvements of psoriasis patients upon secukinumab treatment. |
| title_fullStr | Global circRNA expression changes predate clinical and histological improvements of psoriasis patients upon secukinumab treatment. |
| title_full_unstemmed | Global circRNA expression changes predate clinical and histological improvements of psoriasis patients upon secukinumab treatment. |
| title_short | Global circRNA expression changes predate clinical and histological improvements of psoriasis patients upon secukinumab treatment. |
| title_sort | global circrna expression changes predate clinical and histological improvements of psoriasis patients upon secukinumab treatment |
| url | https://doi.org/10.1371/journal.pone.0275219 |
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