A microRNA focus on acne


Published: 2 February 2024
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Acne (syn. acne vulgaris) is a common inflammatory skin disorder associated with puberty and adolescence. The disease is characterized by comedoneous lesions, papules, pustules, and nodules that are mostly found on the face. These lesions are caused by intricate interactions between the pilosebaceous unit and the Cutibacterium acnes (C. acnes) bacteria. Unhealthy acne and its aftereffects, like pigment changes and scarring, have a detrimental impact on one’s quality of life. Recent years have seen a sharp increase in the approval of nucleic acid therapies (NATs), such as antisense oligonucleotides and short-interfering RNA medications, for rare diseases for which there are few or no effective treatments. These developments suggest that NATs may be useful in acne treatment plans down the road, as do clinical trials for microRNA (miRNA) modulation in skin contexts. We highlight promising miRNA targets for anti-acne therapy in this review. We outline the pathophysiology of acne in brief and emphasize the functions of C. acnes. Next, we concentrate on the distinct impacts of biofilm and planktonic C. acnes on a Toll-like receptor 2 axis that spans miR-146a-5p, which was recently discovered. Before discussing the potential contributions of miR-21- 5p, miR-233-3p, and miR-150-5p to inflammatory axes in acne, we evaluate miR-146a-5p in sebocytes. Finally, we address patient involvement in miRNA-related acne research and translational perspectives.


Proksch E, Brandner JM, Jensen JM. The skin: an indispensable barrier. Exp Dermatol 2008;17:1063-72.

Fitz-Gibbon S, Tomida S, Chiu BH, et al. Propionibacterium acnes strain populations in the human skin microbiome associated with acne. J Invest Dermatol 2013;133:2152-60.

Tomida S, Nguyen L, Chiu BH, et al. Pan-genome and comparative genome analyses of propionibacterium acnes reveal its genomic diversity in the healthy and diseased human skin microbiome. mBio 2013;4:e00003-13.

Rozas M, Hart de Ruijter A, Fabrega MJ, et al. From dysbiosis to healthy skin: major contributions of cutibacterium acnes to skin homeostasis. Microorganisms 2021;9.

Layton AM, Thiboutot D, Tan J. Reviewing the global burden of acne: how could we improve care to reduce the burden? Br J Dermatol 2021;184:219-25.

Hay RJ, Johns NE, Williams HC, et al. The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions. J Invest Dermatol 2014;134:1527-34.

Tayel K, Attia M, Agamia N, Fadl N. Acne vulgaris: prevalence, severity, and impact on quality of life and self-esteem among Egyptian adolescents. J Egypt Public Health Assoc 2020;95:30.

Reljic V, Maksimovic N, Jankovic J, et al. Evaluation of the quality of life in adolescents with acne. Vojnosanit Pregl 2014;71:634-8.

Durovic MR, Durovic M, Jankovic J, Jankovic S. Quality of life in Montenegrin pupils with acne. PLoS One 2021;16:e0250155.

Desai KP, Martyn-Simmons C, Viner R, Segal TY. Help-seeking behaviours, opportunistic treatment and psychological implications of adolescent acne: cross-sectional studies in schools and hospital outpatient departments in the UK. BMJ Open 2017;7:e016964.

Uslu G, Sendur N, Uslu M, et al. Acne: prevalence, perceptions and effects on psychological health among adolescents in Aydin, Turkey. J Eur Acad Dermatol Venereol 2008;22:462-9.

Aksu AE, Metintas S, Saracoglu ZN, et al. Acne: prevalence and relationship with dietary habits in Eskisehir, Turkey. J Eur Acad Dermatol Venereol 2012;26:1503-9.

Kubota Y, Shirahige Y, Nakai K, et al. Community-based epidemiological study of psychosocial effects of acne in Japanese adolescents. J Dermatol 2010;37:617-22.

Bagatin E, Timpano DL, Guadanhim LR, et al. Acne vulgaris: prevalence and clinical forms in adolescents from Sao Paulo, Brazil. An Bras Dermatol 2014;89:428-35.

Ghodsi SZ, Orawa H, Zouboulis CC. Prevalence, severity, and severity risk factors of acne in high school pupils: a community-based study. J Invest Dermatol 2009;129:2136-41.

Lynn DD, Umari T, Dunnick CA, Dellavalle RP. The epidemiology of acne vulgaris in late adolescence. Adolesc Health Med Ther 2016;7:13-25.

Davis EC, Callender VD. A review of acne in ethnic skin: pathogenesis, clinical manifestations, and management strategies. J Clin Aesthet Dermatol 2010;3:24-38.

Smith H, Layton AM, Thiboutot D, et al. Identifying the impacts of acne and the use of questionnaires to detect these impacts: a systematic literature review. Am J Clin Dermatol 2021;22:159-71.

Finkel RS, Chiriboga CA, Vajsar J, et al. Treatment of infantile- onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet 2016;388:3017-26.

Corey DR. Nusinersen, an antisense oligonucleotide drug for spinal muscular atrophy. Nat Neurosci 2017;20:497-9.

Wagner KR, Kuntz NL, Koenig E, et al. Safety, tolerability, and pharmacokinetics of casimersen in patients with Duchenne muscular dystrophy amenable to exon 45 skipping: a randomized, double-blind, placebo-controlled, dose titration trial. Muscle Nerve 2021;64:285-92.

Shirley M. Casimersen: first approval. Drugs 2021;81:875-9.

Gouni-Berthold I, Alexander VJ, Yang Q, et al. Efficacy and safety of volanesorsen in patients with multifactorial chylomicronaemia (COMPASS): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol 2021;9:264-75.

Adams D, Gonzalez-Duarte A, O’Riordan WD, et al. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N Engl J Med 2018;379:11-21.

Balwani M, Sardh E, Ventura P, et al. Phase 3 trial of RNAi therapeutic givosiran for acute intermittent porphyria. N Engl J Med 2020;382:2289-301.

Garrelfs SF, Frishberg Y, Hulton SA, et al. Lumasiran, an RNAi therapeutic for primary hyperoxaluria type 1. N Engl J Med 2021;384:1216-26.

Raal FJ, Kallend D, Ray KK, et al. Inclisiran for the treatment of heterozygous familial hypercholesterolemia. N Engl J Med 2020;382:1520-30.

Adams D, Tournev IL, Taylor MS, et al. Efficacy and safety of vutrisiran for patients with hereditary transthyretin mediated amyloidosis with polyneuropathy: a randomized clinical trial. Amyloid 2022:1-9.

Kulkarni JA, Witzigmann D, Thomson SB, et al. The current landscape of nucleic acid therapeutics. Nat Nanotechnol 2021;16:630-43.

Ross K. MiR equal than others: microRNA enhancement for cutaneous wound healing. J Cell Physiol 2021;236:8050-9.

Bibby G, Krasniqi B, Reddy I, et al. Capturing the RNA castle: exploiting microRNA inhibition for wound healing. FEBS J 2021.

Dykes IM, Ross K. Restoring the final frontier: exosomal microRNA and cutaneous wound repair. Biomol Res Rep 2021;1:1-15.

Li D, Niu G, Landen NX. Beyond the code: noncoding RNAs in skin wound healing. Cold Spring Harb Perspect Biol 2022.

Gallant-Behm CL, Piper J, Lynch JM, et al. A microRNA-29 mimic (Remlarsen) represses extracellular matrix expression and fibroplasia in the skin. J Invest Dermatol 2019;139:1073-81.

Zeng R, Xu H, Liu Y, et al. miR-146a inhibits biofilm-derived cutibacterium acnes-induced inflammatory reactions in human keratinocytes. J Invest Dermatol 2019;139:2488-96 e4.

Ghumra W, Lee N, Whitehouse H, et al. MicroRNAs as biomarkers of atrophic scarring in acne: a cross-sectional analysis of 41 patients. Clin Exp Dermatol 2021;46:1495-503.

Dreno B. What is new in the pathophysiology of acne, an overview. J Eur Acad Dermatol Venereol 2017;31:8-12.

Bruggemann H, Salar-Vidal L, Gollnick HPM, Lood R. A Janus-faced bacterium: host-beneficial and -detrimental roles of cutibacterium acnes. Front Microbiol 2021;12:673845.

Philpott MP. Culture of the human pilosebaceous unit, hair follicle and sebaceous gland. Exp Dermatol 2018;27:571-7.

Byrd AL, Belkaid Y, Segre JA. The human skin microbiome. Nat Rev Microbiol 2018;16:143-55.

Iftikhar U, Choudhry N. Serum levels of androgens in acne & their role in acne severity. Pak J Med Sci 2019;35:146-50.

Williams HC, Dellavalle RP, Garner S. Acne vulgaris. Lancet 2012;379:361-72.

Burkhart CG, Burkhart CN. Expanding the microcomedone theory and acne therapeutics: Propionibacterium acnes bioflim produces biological glue that holds corneocytes together to form plug. J Am Acad Dermatol 2007;57:722-4.

Coenye T, Spittaels KJ, Achermann Y. The role of biofilm formation in the pathogenesis and antimicrobial susceptibility of Cutibacterium acnes. Biofilm 2022;4:100063.

Kuehnast T, Cakar F, Weinhaupl T, et al. Comparative analyses of biofilm formation among different Cutibacterium acnes isolates. Int J Med Microbiol 2018;308:1027-35.

Coenye T, Peeters E, Nelis HJ. Biofilm formation by Propionibacterium acnes is associated with increased resistance to antimicrobial agents and increased production of putative virulence factors. Res Microbiol 2007;158:386-92.

Jahns AC, Lundskog B, Ganceviciene R, et al. An increased incidence of Propionibacterium acnes biofilms in acne vulgaris: a case-control study. Brit J Dermatol 2012;167:50-8.

Jahns AC, Alexeyev OA. Three dimensional distribution of Propionibacterium acnes biofilms in human skin. Exp Dermatol 2014;23:687-9.

Bronnec V, Alexeyev OA. In vivo model of Propionibacterium (Cutibacterium) spp. biofilm in Drosophila melanogaster. Anaerobe 2021;72.

Sun L, Liu W, Zhang LJ. The role of Toll-like receptors in skin host defense, psoriasis, and atopic dermatitis. J Immunol Res 2019;2019:1824624.

Taganov KD, Boldin MP, Chang KJ, Baltimore D. NFkappaB- dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA 2006;103:12481-6.

Dainichi T, Matsumoto R, Mostafa A, Kabashima K. Immune control by TRAF6-mediated pathways of epithelial cells in the EIME (Epithelial Immune Microenvironment). Front Immunol 2019;10:1107.

Meisgen F, Xu Landen N, Wang A, et al. MiR-146a negatively regulates TLR2-induced inflammatory responses in keratinocytes. J Invest Dermatol 2014;134:1931-40.

Dull K, Fazekas F, Deak D, et al. miR-146a modulates TLR1/2 and 4 induced inflammation and links it with proliferation and lipid production via the indirect regulation of GNG7 in human SZ95 sebocytes. Sci Rep 2021;11:21510.

Guinea-Viniegra J, Jimenez M, Schonthaler HB, et al. Targeting miR-21 to treat psoriasis. Sci Transl Med 2014;6:225re1.

Campione E, Mazzotta AM, Bianchi L, Chimenti S. Severe acne successfully treated with etanercept. Acta Derm Venereol 2006;86:256-7.

Sand FL, Thomsen SF. Adalimumab for the treatment of refractory acne conglobata. JAMA Dermatol 2013;149:1306-7.

He Y, Jiang X, Chen J. The role of miR-150 in normal and malignant hematopoiesis. Oncogene 2014;33:3887-93.

Agak GW, Kao S, Ouyang K, et al. Phenotype and antimicrobial activity of Th17 cells induced by propionibacterium acnes strains associated with healthy and acne skin. J Invest Dermatol 2018;138:316-24.

Neamah WH, Singh NP, Alghetaa H, et al. AhR activation leads to massive mobilization of myeloid-derived suppressor cells with immunosuppressive activity through regulation of CXCR2 and microRNA miR-150-5p and miR-543-3p that target anti-inflammatory genes. J Immunol 2019;203:1830-44.

Chang WA, Tsai MJ, Hung JY, et al. miR-150-5p-containing extracellular vesicles are a new immunoregulator that favor the progression of lung cancer in hypoxic microenvironments by altering the phenotype of NK cells. Cancers (Basel) 2021;13.

Johnnidis JB, Harris MH, Wheeler RT, et al. Regulation of progenitor cell proliferation and granulocyte function by microRNA-223. Nature 2008;451:1125-9.

de Kerckhove M, Tanaka K, Umehara T, et al. Targeting miR-223 in neutrophils enhances the clearance of Staphylococcus aureus in infected wounds. EMBO Mol Med 2018;10.

Zhou W, Pal AS, Hsu AY, et al. MicroRNA-223 suppresses the canonical NF-kappaB pathway in basal keratinocytes to dampen neutrophilic inflammation. Cell Rep 2018;22:1810-23.

Lee WJ, Jung HD, Chi SG, et al. Effect of dihydrotestosterone on the upregulation of inflammatory cytokines in cultured sebocytes. Arch Dermatol Res 2010;302:429-33.

Philippe L, Alsaleh G, Suffert G, et al. TLR2 expression is regulated by microRNA miR-19 in rheumatoid fibroblast-like synoviocytes. J Immunol 2012;188:454-61.

Li Z, Cai J, Cao X. MiR-19 suppresses fibroblast-like synoviocytes cytokine release by targeting toll like receptor 2 in rheumatoid arthritis. Am J Transl Res 2016;8:5512-8.

Gantier MP, Stunden HJ, McCoy CE, et al. A miR-19 regulon that controls NF-kappaB signaling. Nucleic Acids Res 2012;40:8048-58.

Bonora GM, Scremin CL, Colonna FP, Garbesi A. HELP (high efficiency liquid phase) new oligonucleotide synthesis on soluble polymeric support. Nucleic Acids Res 1990;18:3155-9.

Bonora GM, Biancotto G, Maffini M, Scremin CL. Large scale, liquid phase synthesis of oligonucleotides by the phosphoramidite approach. Nucleic Acids Res 1993;21:1213-7.

Padiya KJ, Salunkhe MM. Large scale, liquid phase oligonucleotide synthesis by alkyl H-phosphonate approach. Bioorg Med Chem 2000;8:337-42.

Molina AG, Sanghvi YS. Liquid-phase oligonucleotide synthesis: past, present, and future predictions. Curr Protoc Nucleic Acid Chem 2019;77:e82.

Hong DS, Kang YK, Borad M, et al. Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours. Br J Cancer 2020;122:1630-7.

Ross K. Towards topical microRNA-directed therapy for epidermal disorders. J Control Release 2018;269:136-47.

Mandal A, Kumbhojkar N, Reilly C, et al. Treatment of psoriasis with NFKBIZ siRNA using topical ionic liquid formulations. Sci Adv 2020;6:eabb6049.

Biscans A, Caiazzi J, McHugh N, et al. Docosanoic acid conjugation to siRNA enables functional and safe delivery to skeletal and cardiac muscles. Mol Ther 2021;29:1382-94.

Francis NA, Entwistle K, Santer M, et al. The management of acne vulgaris in primary care: a cohort study of consulting and prescribing patterns using the Clinical Practice Research Datalink. Br J Dermatol 2017;176:107-15.

NICE. Acne vulgaris: management. NICE guideline [NG198]. 2021.

Layton AM, Henderson CA, Cunliffe WJ. A clinical evaluation of acne scarring and its incidence. Clin Exp Dermatol 1994;19:303-8.

Tan J, Thiboutot D, Gollnick H, et al. Development of an atrophic acne scar risk assessment tool. J Eur Acad Dermatol Venereol 2017;31:1547-54.

Layton A, Eady EA, Peat M, et al. Identifying acne treatment uncertainties via a James Lind Alliance Priority Setting Partnership. BMJ Open 2015;5:e008085.

Santer M, Francis NA, Platt D, et al. Stemming the tide of antimicrobial resistance: implications for management of acne vulgaris. Br J Gen Pract 2018;68:64-5.

Karadag AS, Aslan Kayiran M, Wu CY, et al. Antibiotic resistance in acne: changes, consequences and concerns. J Eur Acad Dermatol Venereol 2021;35:73-8.

Padda IS, Mahtani AU, Parmar M. Small Interfering RNA (siRNA) Based Therapy. StatPearls. Treasure Island (FL); 2023.

Gordon, S., Layton, A. M., Fawcett, S., & Ross, K. (2024). A microRNA focus on acne. Dermatology Reports, 16(2). https://doi.org/10.4081/dr.2024.9902

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