lncRNA TINCR participates in ALA-PDT-induced apoptosis and autophagy in cutaneous squamous cell carcinoma

J Cell Biochem. 2019 Aug;120(8):13893-13902. doi: 10.1002/jcb.28662. Epub 2019 Apr 16.

Abstract

This study aims to investigate whether terminal differentiation-induced ncRNA (TINCR) has an effect on apoptosis and autophagy induced by ALA-PDT in cutaneous squamous cell carcinoma (CSCC). A431 cells were treated with 5-aminolevulinic acid (ALA) solution at different concentrations and for different duration time. A431 cell viability was detected by Cell Counting Kit-8 (CCK-8) assay, relative TINCR messenger RNA expression was detected by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). A431 cell apoptosis was examined by flow cytometry. Relative apoptosis/autophagy-related protein expression was analyzed by Western blot analysis. The effect of TINCR on cell autophagy was detected by RFP-LC3 immunofluorescence assay. Reactive oxygen species concentration was detected by 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe. Relative expressions of ERK1/2 and specificity protein 3 (Sp3) in A43 cells were detected by Western blot analysis and qRT-PCR. Sp3 binding sites were analyzed by ChIP-qPCR. The relative transcription activity was measured with luciferase reporter assay. ALA-PDT treatment at 3.2 mmol/L for 120 minutes significantly promoted TINCR expression in CSCC A431 cells, and TINCR promoted ALA-PDT-induced apoptosis and cell autophagy. Furthermore, ALA-PDT promoted TINCR expression through ERK1/2-SP3 pathway. Sp3 promoted TINCR transcription by binding TINCR promoters. Our data indicated that TINCR involves in ALA-PDT-induced apoptosis and autophagy in CSCC.

Keywords: ERK1/2-Sp3 pathway; apoptosis; autophagy; terminal differentiation-induced ncRNA.

MeSH terms

  • Aminolevulinic Acid / pharmacology
  • Aminolevulinic Acid / therapeutic use*
  • Apoptosis* / drug effects
  • Apoptosis* / genetics
  • Autophagy* / drug effects
  • Autophagy* / genetics
  • Base Sequence
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Photochemotherapy*
  • Promoter Regions, Genetic / genetics
  • Protein Binding / drug effects
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology
  • Sp3 Transcription Factor / metabolism
  • Transcription, Genetic / drug effects

Substances

  • RNA, Long Noncoding
  • TINCR lncRNA, human
  • Sp3 Transcription Factor
  • Aminolevulinic Acid