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LncRNA PROX1 antisense RNA 1 promotes PD-L1-mediated proliferation, metastasis, and immune escape in colorectal

Jian-Sheng Li1, Tong-Ming Liu2, Li Li3

  • 1Department of Anorectal Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan.

Anti-Cancer Drugs
|February 2, 2023
PubMed

Insights

Long non-coding RNA PROX1-AS1 promotes colorectal cancer (CRC) progression and immune evasion by targeting miR-520d to upregulate PD-L1. Inhibiting PROX1-AS1 suppressed tumor growth and enhanced anti-tumor immunity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Long non-coding RNA PROX1 antisense RNA 1 (PROX1-AS1) exhibits oncogenic properties in various cancers.
  • Understanding the role of PROX1-AS1 in colorectal cancer (CRC) pathogenesis and immune evasion is crucial.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying PROX1-AS1's function in CRC development.
  • To investigate the involvement of PROX1-AS1 in CRC-associated immune evasion.

Main Methods:

  • Analysis of PROX1-AS1 and PD-L1 expression in CRC tissues and cells.
  • In vitro assays assessing CRC cell proliferation, migration, and invasion upon PROX1-AS1 interference.
  • Evaluation of CD8+ T-lymphocyte apoptosis, cytotoxicity, and percentage.
  • In vivo studies involving PROX1-AS1 deletion in a CRC tumor model.
  • Investigation of the interaction between PROX1-AS1, miR-520d, and PD-L1.

Main Results:

  • PROX1-AS1 and PD-L1 expression levels were elevated in CRC tissues and cells.
  • PROX1-AS1 inhibition significantly reduced CRC cell proliferation, migration, and invasion.
  • PROX1-AS1 interference led to decreased CD8+ T-lymphocyte apoptosis and increased cytotoxicity and percentage.
  • PROX1-AS1 was found to absorb miR-520d, consequently upregulating PD-L1 expression.
  • PROX1-AS1 deletion impaired tumor growth in vivo.

Conclusions:

  • PROX1-AS1 promotes colorectal cancer progression and immune escape by sponging miR-520d and upregulating PD-L1.
  • Targeting PROX1-AS1 represents a potential therapeutic strategy for CRC, enhancing anti-tumor immunity.

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