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Long noncoding RNA TTN-AS1 facilitates tumorigenesis and metastasis by maintaining TTN expression in skin cutaneous

Ying Wang1,2, Dongping Li1,2, Jiqiang Lu1,2

  • 1The Engineering Research Center of Synthetic Peptide Drug Discovery and Evaluation of Jiangsu Province, China Pharmaceutical University, Nanjing, 210009, China.

Cell Death & Disease
|August 22, 2020
PubMed

Insights

Long noncoding RNA TTN-AS1 promotes skin cutaneous melanoma (SKCM) by increasing titin (TTN) expression. High TTN-AS1 and TTN levels correlate with poor SKCM patient survival, suggesting potential therapeutic targets.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Antisense transcripts play crucial roles in gene regulation.
  • Long noncoding RNAs (lncRNAs) are increasingly recognized for their involvement in various biological processes, including cancer.

Purpose of the Study:

  • To investigate the role of lncRNA-TTN-AS1 in skin cutaneous melanoma (SKCM).
  • To explore the molecular mechanisms by which lncRNA-TTN-AS1 influences SKCM progression.
  • To assess the clinical significance of lncRNA-TTN-AS1 and its correlation with titin (TTN) in SKCM.

Main Methods:

  • Correlation analysis of TTN and lncRNA-TTN-AS1 expression in SKCM cells.
  • In vitro and in vivo functional assays to assess the impact of TTN-AS1 and TTN on SKCM tumorigenesis and metastasis.
  • Investigation of the epigenetic regulation of lncRNA-TTN-AS1 expression (hypomethylation).
  • Analysis of TTN promoter activity and TTN mRNA stability.
  • Clinical correlation analysis with patient survival data.

Main Results:

  • A significant positive correlation was observed between TTN and lncRNA-TTN-AS1 expression in SKCM.
  • Ectopic expression of TTN-AS1 and TTN promoted SKCM tumorigenesis and metastasis.
  • Knockdown of TTN partially reversed the pro-tumorigenic effects of lncRNA-TTN-AS1.
  • High expression of lncRNA-TTN-AS1 was linked to hypomethylation of its transcription initiation site.
  • LncRNA-TTN-AS1 enhanced TTN expression transcriptionally and post-transcriptionally by increasing TTN promoter activity and TTN mRNA stability.
  • High TTN and lncRNA-TTN-AS1 expression correlated with poor overall survival in SKCM patients.

Conclusions:

  • LncRNA-TTN-AS1 promotes SKCM progression by upregulating TTN expression via epigenetic modifications and mRNA stabilization.
  • LncRNA-TTN-AS1 and TTN represent potential novel biomarkers and therapeutic targets for SKCM.

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