Deregulated Long Non-Coding RNAs (lncRNA) as Promising Biomarkers in Hidradenitis Suppurativa

Author:

Radhakrishna Uppala1ORCID,Ratnamala Uppala2,Jhala Devendrasinh D.3ORCID,Uppala Lavanya V.4,Vedangi Aaren5,Saiyed Nazia6,Patel Maulikkumar7ORCID,Shah Sushma R.8,Rawal Rakesh M.2,Jemec Gregor B. E.9,Mazza Tommaso10ORCID,Mazzoccoli Gianluigi11ORCID,Damiani Giovanni121314ORCID

Affiliation:

1. Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA

2. Department of Life Sciences, School of Sciences, Gujarat University, Ahmedabad 380009, India

3. Department of Zoology, School of Sciences, Gujarat University, Ahmedabad 380009, India

4. Peter Kiewit Institute, College of Information Science & Technology, The University of Nebraska at Omaha, Omaha, NE 68182, USA

5. Department of Clinical Research, KIMS ICON Hospital, ICON Krishi Institute Medical Sciences, Sheelanagar, Visakhapatnam 530012, India

6. Department of Obstetrics and Gynecology, Corewell Health William Beaumont University Hospital, Royal Oak, MI 48073, USA

7. Bioinformatics Unit, Gujarat University, Ahmedabad 380009, India

8. Department of Obstetrics and Gynecology, BJ Medical College Institute of Medical Post-Graduate Studies and Research, Ahmedabad 380016, India

9. Department of Dermatology, Zealand University Hospital, 4000 Roskilde, Denmark

10. Bioinformatics Unit, IRCCS “Casa Sollievo della Sofferenza”, Opera di Padre Pio da Pietrelcina, Cappuccini Avenue, 71013 San Giovanni Rotondo, Italy

11. Division of Internal Medicine and Chronobiology Laboratory, Department of Medical Sciences, IRCCS “Casa Sollievo della Sofferenza”, Opera di Padre Pio da Pietrelcina, 71013 San Giovanni Rotondo, Italy

12. Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy

13. Italian Center of Precision Medicine and Chronic Inflammation, University of Milan, 20122 Milan, Italy

14. Fondazione IRCCS Ca’ Granda, Ospedale maggiore Policlinico, 20122 Milan, Italy

Abstract

Background/Objectives: In recent times, epigenetics alterations in Hidradenitis suppurativa (HS) have been explored and exploited translationally to guide investigation of new therapeutic approaches. On the other hand, long noncoding RNAs (LncRNAs), main regulators of the epigenetic status of the human genome, have been scarcely investigated, notwithstanding their potential relevance in broad pathogenesis comprehension. Here, we aim to explore the methylation pattern of lncRNAs in HS. Methods: In this case-control study, 24 HS patients and age-, sex- and BMI-matched controls were analyzed to characterize the methylome of lncRNA genes in peripheral blood cells. Gene ontology analysis (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein–protein interaction (PPI) network, and MCODE analysis were performed. Results: A set of fifteen lncRNA genes exhibited significantly differential methylation patterns, with ten of them showing hypomethylation and five displaying hypermethylation at specific CpG sites. The hypomethylated lncRNA genes were DLEU2, MESTIT1, CASC2, TUG1, KCNQ1DN, PSORS1C3, PCA3, DSCR8, RFPL1S, and PVT1, while the hypermethylated ones were HAR1A, FAM66B, SNHG9, HCG9, and HCP5. These lncRNA genes have been linked to various important biological processes, including cell proliferation, apoptosis, inflammation, chronic inflammatory skin diseases, and wound healing. Their altered methylation status suggests potential roles in regulating these processes, and may contribute to HS pathogenesis and healing mechanisms. Conclusions: This study revealed an interesting dysregulation pattern of definite lncRNAs in the methylome which is linked to both the development of HS and its comorbidities. Epigenetically altered lncRNAs genes could represent useful biomarkers, and could help in guiding innovative treatment strategies.

Publisher

MDPI AG

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