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Updated: Jul 21, 2025

SUMO-Binding Entities SUBEs as Tools for the Enrichment, Isolation, Identification, and Characterization of the SUMO Proteome in Liver Cancer
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Regulation of hPCL3 isoforms' ubiquitination by TRIM21 in non-small cell lung cancer progression

Ye Xu1, Wenhong Liu1, Xiawei Jiang1

  • 1Department of Immunology and Microbiology, School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.

Life Science Alliance
|July 28, 2023
PubMed

Insights

This study reveals that both hPCL3S and hPCL3L impact non-small cell lung cancer (NSCLC) progression. Targeting hPCL3S shows promise for NSCLC therapy due to its degradation pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Non-small cell lung cancer (NSCLC) is the predominant form of lung cancer.
  • The specific roles of hPCL3 isoforms, hPCL3S and hPCL3L, in NSCLC pathogenesis are not well understood.

Purpose of the Study:

  • To investigate the functional significance of hPCL3S and hPCL3L in NSCLC.
  • To elucidate the regulatory mechanisms involving TRIM21 and hPCL3 isoforms in NSCLC cells.

Main Methods:

  • In vivo and in vitro analyses using NSCLC cell lines (A549, NCI-H226c).
  • Assessment of hPCL3 isoform expression, cell proliferation, invasion, and migration.
  • Investigation of TRIM21 interaction and ubiquitination of hPCL3 isoforms.

Main Results:

  • Elevated hPCL3S and hPCL3L expression correlate with reduced patient survival.
  • hPCL3S levels are significantly increased in clinical NSCLC specimens.
  • Inhibition of hPCL3S or hPCL3L reduces NSCLC cell proliferation, invasion, and migration, with hPCL3S knockdown being more effective.
  • TRIM21 interacts with both isoforms, mediating hPCL3S degradation via K48-linked ubiquitination, but not hPCL3L degradation.

Conclusions:

  • hPCL3S and hPCL3L exhibit distinct roles in NSCLC progression.
  • TRIM21-mediated degradation of hPCL3S represents a potential therapeutic vulnerability in NSCLC.
  • Targeting hPCL3S may offer a novel therapeutic strategy for NSCLC treatment.

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