SP1-induced PROX1-AS1 contributes to tumor progression by regulating miR-326/FBXL20 axis in colorectal cancer

Cell Signal. 2023 Jan:101:110503. doi: 10.1016/j.cellsig.2022.110503. Epub 2022 Oct 29.

Abstract

Long noncoding RNAs (lncRNAs) play pivotal roles in cancers by regulating tumorigenesis and metastasis. LncRNA PROX1-AS1 has been reported to be involved in tumor progression, however, its role in colorectal cancer (CRC) remains ambiguous. Based on TCGA and GTEx databases, we found that the expression of PROX1-AS1 was upregulated in CRC tissues and cells. Bioinformatics analysis revealed that high PROX1-AS1 expression was associated with poor overall survival. Functionally, PROX1-AS1 knockdown suppressed CRC cell proliferation, migration, and invasion in vitro, as well as inhibiting tumor growth in vivo. Mechanistically, PROX1-AS1 was identified to act as a miR-326 sponge by luciferase reporter and RIP assay. Meanwhile, we found that the transcription factor SP1 activated PROX1-AS1/miR-32/FBXL20 axis, thereby promoting CRC progression. Our data demonstrated that PROX1-AS1 served as a promising prognostic biomarker for CRC, and the potential mechanism was unraveled.

Keywords: Colorectal cancer; FBXL20; PROX1-AS1; SP1; miR-326.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colorectal Neoplasms* / pathology
  • F-Box Proteins* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Sp1 Transcription Factor / genetics
  • Sp1 Transcription Factor / metabolism

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • SP1 protein, human
  • Sp1 Transcription Factor
  • FBXL20 protein, human
  • F-Box Proteins
  • MIRN326 microRNA, human