LncRNA BASP1-AS1 interacts with YBX1 to regulate Notch transcription and drives the malignancy of melanoma

Cancer Sci. 2021 Nov;112(11):4526-4542. doi: 10.1111/cas.15140. Epub 2021 Sep 29.

Abstract

Melanoma is a fatal skin malignant tumor with a poor prognosis. We found that long noncoding RNA BASP1-AS1 is essential for the development and prognosis of melanoma. The methylation, RNA sequencing, copy number variation, mutation data, and sample follow-up information of melanoma from The Cancer Genome Atlas (TCGA) were analyzed using weighted gene co-expression network analysis and 366 samples common to the three omics were selected for multigroup clustering analysis. A four-gene prognostic model (BASP1-AS1, LOC100506098, ARHGAP27P1, and LINC01532) was constructed in the TCGA cohort and validated using the GSE65904 series. The expression of BASP1-AS1 was upregulated in melanoma tissues and various melanoma cell lines. Functionally, the ectopic expression of BASP1-AS1 promoted cell proliferation, migration, and invasion in both A375 and SK-MEL-2 cells. Mechanically, BASP1-AS1 interacted with YBX1 and recruited it to the promoter of NOTCH3, initiating its transcription process. The activation of the Notch signaling then resulted in the transcription of multiple oncogenes, including c-MYC, PCNA, and CDK4, which contributed to melanoma progression. Thus, BASP1-AS1 could act as a potential biomarker for cutaneous malignant melanoma.

Keywords: BASP1-AS1; NOTCH3; YBX1; melanoma; signature.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • GTPase-Activating Proteins / metabolism
  • Gene Silencing
  • Humans
  • Male
  • Melanoma / metabolism*
  • Melanoma / mortality
  • Melanoma / pathology
  • Melanoma, Cutaneous Malignant
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Murine pneumonia virus
  • Neoplasm Invasiveness
  • Neoplasm Proteins / metabolism
  • Neoplasm Transplantation
  • Neoplastic Stem Cells
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Long Noncoding / metabolism*
  • Random Allocation
  • Receptor, Notch3 / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology
  • Transcription, Genetic
  • Up-Regulation
  • Y-Box-Binding Protein 1 / metabolism*

Substances

  • ARHGAP27 protein, human
  • BASP1 protein, human
  • GTPase-Activating Proteins
  • Membrane Proteins
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Long Noncoding
  • Receptor, Notch3
  • Repressor Proteins
  • Y-Box-Binding Protein 1
  • YBX1 protein, human