2. Academic Validation
  3. Elevated SNHG15 empowers keratinocytes hyperproliferation through activation of STAT3/Cyclin D1 axis in psoriasis

Elevated SNHG15 empowers keratinocytes hyperproliferation through activation of STAT3/Cyclin D1 axis in psoriasis

  • Acta Pharm Sin B. 2025 Dec;15(12):6430-6443. doi: 10.1016/j.apsb.2025.10.010.
Lipeng Tang 1 2 3,  Guanzhuo Li 3,  Jiameng Chang 3,  Haiyan Xian 3,  Yanjie Liu 4,  Luping Lin 5,  Zixin Dai 5,  Zhenting Liu 5,  Xinmin Qiu 6,  Bowen Zhang 2 3,  Zuqing Su 2 3,  Bing Feng 2 3,  Ying Zhu 2 3,  Maojie Wang 7,  Yuchao Chen 8,  Huazhen Liu 8,  Dinghong Wu 9,  Chutian Li 10,  Jie Zhao 10,  Mingxian Li 10,  Yongzhan Zhu 10,  Xingyi Xie 10,  Hao Deng 11,  Shuyan Ye 11,  Shicheng Fan 12,  Huichang Bi 12,  Chuanjian Lu 1 2 11,  Guangjuan Zheng 1 2 3 10
Affiliations

Affiliations

  • 1 State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510000, China.
  • 2 Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510000, China.
  • 3 Department of Pharmacology of Traditional Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510000, China.
  • 4 Department of Dermatology, The Seventh Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen 518000, China.
  • 5 School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China.
  • 6 Genetic Testing Lab, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510000, China.
  • 7 Department of Rheumatology Clinical and Basic Research, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510000, China.
  • 8 Department of Immunology, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510000, China.
  • 9 Department of Material Basis of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510000, China.
  • 10 Department of Pathology, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510000, China.
  • 11 Department of Dermatology, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510000, China.
  • 12 NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
PMID: 41477326 DOI: 10.1016/j.apsb.2025.10.010
Abstract

Psoriasis is a common inflammatory skin disease with characterization of epidermal hyperplasia and sustained skin inflammation. Long noncoding RNAs (lncRNAs), which contain more than 200 nucleotide-long transcripts, are emerging as the crux of epigenetic regulators in multiple biological processes and diseases. However, how lncRNAs contribute to the etiology of psoriasis remains to be elucidated. For the first time, this study revealed that SNHG15, which was elevated in cytokines-stimulated keratinocytes and psoriasis lesions, promoted keratinocytes hyperproliferation. Mechanistically, SNHG15 fueled epithelial pathology through activation of STAT3/Cyclin D1 axis. Intriguingly, activation of STAT3 enhanced SNHG15 transcription to form a positive feed-back modulatory loop and consequently augmented the skin lesions in psoriasis. Furthermore, knock down the expression of SNHG15 can counteract the IMQ-induced keratinocytes hyperproliferation in vivo. Taken together, our findings uncover that SNHG15 facilitates epidermal hyperplasia via STAT3/Cyclin D1 axis, which might provide a novel therapeutic avenue for psoriasis treatment.

Keywords

Cell proliferation; Cyclin D1; Keratinocytes; Long noncoding RNAs; Psoriasis; RNA interference therapy; SNHG15; STAT3.

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