A Peptide Encoded by a Long Non-Coding RNA DLX6-AS1 Facilitates Cell Proliferation, Migration, and Invasion by Activating the wnt/β-Catenin Signaling Pathway in Non-Small-Cell Lung Cancer Cell

Crit Rev Eukaryot Gene Expr. 2022;32(8):43-53. doi: 10.1615/CritRevEukaryotGeneExpr.2022043172.

Abstract

Recently, accumulating study shows that some long non-coding RNAs (lncRNAs) have potential protein/peptide-coding capacities. In this study, the coding potential of lncRNA distal-less homeobox 6 antisense 1 (DLX6-AS1) was examined and the roles and downstream pathways of a DLX6-AS1-encoded peptide in non-small-cell lung cancer (NSCLC) cell development were investigated. The peptide-coding potential of lncRNA DLX6-AS1 was extrapolated based on prior ribosome footprint and ribosome sequencing data, IPX0002962000 mass spectrometry dataset, and Getorf bioinformatics analysis. The peptide-coding abilities of several DLX6-AS1 open reading frame (ORF) fragments, as well as protein levels were detected by Western blot assay. Cell proliferative, migratory, and invasive abilities were tested by CCK-8 or Transwell assays, respectively. Potential key biological processes and pathways related to DLX6-AS1 expression were identified by single-gene gene set enrichment analysis (GSEA) based on RNA-seq data of 510 lung adenocarcinoma samples in the TCGA GDC database. The results showed that an ORF of lncRNA DLX6-AS1 could encode a short peptide. The exogenous overexpression of this ORF-encoded peptide promoted NSCLC cell proliferation, migration, and invasion. GSEA analysis suggested that DLX6-AS1 might play crucial roles in cancer progression and wnt signaling pathway. Further analysis revealed that the exogenous overexpression of a DLX6-AS1-encoded peptide could exert its functions by activating the wnt/β-catenin pathway in NSCLC cells. In conclusion, the exogenous overexpression of a DLX6-AS1-encoded peptide could facilitate NSCLC cell growth by activating wnt/β-catenin pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Lung
  • Lung Neoplasms* / genetics
  • MicroRNAs* / genetics
  • Peptides / genetics
  • Peptides / metabolism
  • RNA, Long Noncoding* / genetics
  • Wnt Signaling Pathway / genetics
  • beta Catenin / genetics

Substances

  • Homeodomain Proteins
  • MicroRNAs
  • Peptides
  • RNA, Long Noncoding
  • beta Catenin