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The RNA-binding protein PCBP1 represses lung adenocarcinoma progression by stabilizing DKK1 mRNA and subsequently

Yujia Zheng1, Zheng Zhou1, Ran Wei2

  • 1Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Journal of Translational Medicine
|July 30, 2022
PubMed
Abstract

Insights

PolyC-RNA-binding protein 1 (PCBP1) acts as a tumor suppressor in lung adenocarcinoma (LUAD). Downregulation of PCBP1 promotes LUAD cell proliferation and migration by stabilizing DKK1 mRNA, inactivating the Wnt/β-catenin pathway.

Area of Science:

  • Molecular Biology
  • Oncology
  • Gene Regulation

Background:

  • PolyC-RNA-binding protein 1 (PCBP1) is a known tumor suppressor and RNA regulator.
  • PCBP1 expression is frequently downregulated in various human cancers.
  • The specific role of PCBP1 in lung adenocarcinoma (LUAD) requires further elucidation.

Purpose of the Study:

  • To investigate the biological function and molecular mechanisms of PCBP1 in LUAD.
  • To determine if PCBP1 acts as a tumor suppressor in LUAD.
  • To identify downstream targets and pathways regulated by PCBP1 in LUAD.

Main Methods:

  • Bioinformatic analysis using The Cancer Genome Atlas (TCGA) to identify PCBP1 as a LUAD biomarker.
  • In vitro assays including colony formation, CCK8, cell proliferation, wound healing, and Transwell assays to assess cell behavior.
  • RNA sequencing, western blot, qPCR, RIP, RNA pulldown, and mRNA stability assays to elucidate molecular mechanisms.

Main Results:

  • PCBP1 is significantly downregulated in LUAD tissues.
  • Reduced PCBP1 expression enhances LUAD cell proliferation, migration, and invasion in vitro and in vivo.
  • PCBP1 directly binds to and stabilizes DKK1 mRNA, thereby repressing LUAD progression.

Conclusions:

  • PCBP1 functions as a tumor suppressor in LUAD by upregulating DKK1 and consequently inhibiting the Wnt/β-catenin signaling pathway.
  • PCBP1 downregulation promotes LUAD tumorigenesis.
  • PCBP1 represents a potential therapeutic target for LUAD treatment.
Keywords:
DKK1LUADPCBP1Wnt signalling pathway

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