Role of the long non-coding RNA, SPRR2C, based on an in vitro psoriatic keratinocyte cell model

Eur J Dermatol. 2022 Apr 1;32(2):171-180. doi: 10.1684/ejd.2022.4247.

Abstract

Background: Psoriasis is a chronic inflammatory disease of the skin with complex pathogenesis. Long non-coding RNAs (lncRNAs) play an important regulatory role in the occurrence and progression of many diseases, as well as psoriasis.

Objectives: This study aimed to investigate the role and mechanism of the lncRNA, SPRR2C, in M5-induced psoriatic keratinocytes.

Materials & methods: SPRR2C expression and subcellular localization was detected using FISH and qRT-PCR. Ker-CT and HaCaT cells stimulated by M5 (IL-17A, tumour necrosis factor-α, IL-1α, IL-22, and oncostatin-M) were used to establish a psoriatic cell model. CCK-8 assay, CFSE proliferation assay, flow cytometry, western blotting and ELISA were used to examine the effects of SPRR2C in the keratinocyte model.

Results: SPRR2C was highly expressed in psoriatic samples and M5-induced psoriatic keratinocytes, and SPRR2C was mainly localised to the cytoplasm. In keratinocytes, SPRR2C regulated proliferation, cell cycle and apoptosis, and induced the expression of IL-1β, IL-6, IL-8, CXCL2 and CCL20. Moreover, SPRR2C cellular effects were shown to be mediated by the PI3K/AKT/mTOR signalling pathway, based on experiments with the AKT-specific inhibitor, MK-2206, which was also shown to suppress overexpression of SPRR2C.

Conclusion: Our results indicate that SPRR2C plays a regulatory role and is involved in the PI3K/AKT/mTOR signalling pathway in psoriatic keratinocytes, which may provide a potential diagnostic and therapeutic target for psoriasis.

Keywords: psoriasis; LncRNA SPRR2C; HaCaT; Ker-CT; proliferation; inflammation.

MeSH terms

  • Cell Proliferation / genetics
  • Cornified Envelope Proline-Rich Proteins / metabolism
  • Humans
  • Keratinocytes / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphatidylinositol 3-Kinases / pharmacology
  • Phosphatidylinositol 3-Kinases / therapeutic use
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-akt / pharmacology
  • Psoriasis* / drug therapy
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • RNA, Long Noncoding* / pharmacology
  • TOR Serine-Threonine Kinases / metabolism
  • TOR Serine-Threonine Kinases / pharmacology
  • TOR Serine-Threonine Kinases / therapeutic use

Substances

  • Cornified Envelope Proline-Rich Proteins
  • RNA, Long Noncoding
  • SPRR2C protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases