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Combined Conditional Knockdown and Adapted Sphere Formation Assay to Study a Stemness-Associated Gene of Patient-derived Gastric Cancer Stem Cells
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Tumour protein p53-activated lncRNA PGM5-AS1 suppresses lung cancer growth and stemness by targeting R-spondin1 via

Peng Yang1, Hong Gu1, Xuanqin Wu1

  • 1Department of Cardiothoracic and Vascular Surgery, Shenzhen Guangming District People's Hospital, Shenzhen, Guangdong, China.

Archives of Physiology and Biochemistry
|March 4, 2025
PubMed
Abstract

Insights

Tumour protein p53 (TP53)-activated PGM5-AS1 inhibits lung cancer (LC) cell growth and stemness by sponging miR-1247-5p, targeting R-spondin1 (RSPO1). This pathway offers a new therapeutic strategy for lung cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Lung cancer (LC) remains a leading cause of cancer-related mortality worldwide.
  • Understanding the molecular mechanisms driving LC progression and therapeutic resistance is crucial.

Purpose of the Study:

  • To investigate the inhibitory role of the tumour protein p53 (TP53)-activated PGM5-AS1 in lung cancer (LC) cell proliferation, invasion, and cancer stem cell (CSC)-like properties.
  • To elucidate the underlying molecular mechanisms involving TP53, PGM5-AS1, miR-1247-5p, and R-spondin1 (RSPO1).

Main Methods:

  • Assessed the effect of PGM5-AS1 on LC cell development, including stem cell markers, aldehyde dehydrogenase activity, and spheroid formation.
  • Determined the interaction between PGM5-AS1 and TP53.
  • Verified the binding interactions of PGM5-AS1, miR-1247-5p, and RSPO1.

Main Results:

  • PGM5-AS1 expression was elevated by the combined action of TP53 and PGM5-AS1 promoters.
  • PGM5-AS1 acted as a molecular sponge for miR-1247-5p in LC cells, and miR-1247-5p targeted RSPO1.
  • Upregulating PGM5-AS1 or downregulating miR-1247-5p inhibited LC cell growth and stemness, effects reversed by RSPO1 downregulation.

Conclusions:

  • TP53-activated PGM5-AS1 inhibits lung cancer growth and stemness by modulating the miR-1247-5p/RSPO1 axis.
  • This pathway represents a potential novel therapeutic target for lung cancer treatment.
Keywords:
LncRNA PGM5-AS1Lung cancerMiR-1247-5pRSPO1TP53

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