A novel long noncoding RNA located on the antisense strand of MAL promotes the invasion and metastasis of oral squamous cell carcinoma

Arch Oral Biol. 2023 Nov:155:105790. doi: 10.1016/j.archoralbio.2023.105790. Epub 2023 Aug 16.

Abstract

Objectives: This study aims to investigate the role of the long non-coding RNA-AC103563.8 (lncRNA) in promoting oral squamous cell carcinoma (OSCC) development and to conduct preliminary research on its mechanism.

Design: Microarray technology were used to screen out a lncRNA significantly upregulated in OSCC. Fluorescence in situ hybridization was used to analyze the position of lncRNA-AC103563.8 in cells. A Cal-27 cell line with knockout of the lncRNA-AC103563.8 gene was constructed. Transwell assay and tumor xenograft experiment was used to determine the metastasis and invasion of the cell. Detection of mutations in genes encoding myelin and lymphocyte proteins (MAL) by pyrosequencing. Identification of RNA-Binding Proteins by Mass Spectrometry (ChIRP-MS) experiments were carried out to enrich the proteins that directly bind to lncRNA-AC103563.8. Bioinformatics was used to analyze the target proteins. Some of the selected proteins were verified by parallel reaction monitoring (PRM) to confirm their binding to lncRNA-AC103563.8.

Results: lncRNA-AC103563.8 is upregulated in OSCC tissue and the presence of lncRNA-AC103563.8 in both the nucleus and the cytoplasm. lncRNA-AC103563.8 promoted OSCC cell invasion and metastasis. Methylation occurs in MAL gene promoter. ChIRP-MS identified 330 proteins binding to lncRNA-AC103563.8, and bioinformatics analysis showed that they were involved in a variety of biological processes. PRM experiments confirmed some protein directly bound to lncRNA-AC103563.8.

Conclusion: lncRNA-AC103563.8 is a functional lncRNA that promotes OSCC development by acting on MAL or interacting with other tumor-related proteins. This study also indicates that this lncRNA may exert regulatory functions in OSCC and is a potential target for OSCC therapy.

Keywords: Invasion; Long noncoding RNA; MAL; Metastasis; Oral cancer.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • In Situ Hybridization, Fluorescence
  • MicroRNAs* / genetics
  • Mouth Neoplasms* / genetics
  • Mouth Neoplasms* / pathology
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Squamous Cell Carcinoma of Head and Neck* / genetics
  • Squamous Cell Carcinoma of Head and Neck* / pathology

Substances

  • MicroRNAs
  • RNA, Long Noncoding