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Cited by 41Circular RNAs in diseasesLung Cancer Research StudiesCancer-related molecular mechanisms research

PLCG2 can exist in eccDNA and contribute to the metastasis of non-small cell lung cancer by regulating mitochondrial respiration

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Yang, Yongfeng, Yang, Ying, Huang, Hong, Song, Tingting, Mao, Shengqiang, Liu, Dan, Zhang, Li, Li, Weimin·2023·Cell Death & Disease
DOI 10.1038/s41419-023-05755-7PMC PMC10082821
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Abstract

Extrachromosomal circular DNAs (eccDNAs) participate in tumorigenesis and tumor progression. However, the role and mechanism of eccDNAs have yet to be elucidated in non-small cell lung cancer (NSCLC). In our research, three surgically matched NSCLC tissue samples, NSCLC cell lines (H1299, A549, and H460), and a normal lung cell line (MRC-5) were used as study objects. High-throughput eccDNA sequencing and bioinformatics analysis were performed to study the distribution pattern and level of eccDNA expression. The upregulated candidate eccDNA-encoding PLCG2 was validated by routine PCR. Plasmid transfection, RNA interference, qRT‒PCR and western blotting experiments were used to verify the expression level of PLCG2. Our results showed that the chromosome distribution, length distribution, and genomic annotation of the eccDNAs were comparable between the NSCLC and normal groups. Nevertheless, there were no significant differences in eccDNAs between NSCLC tissues and matched normal lung tissues. The eccDNA derived from PLCG2 was upregulated in NSCLC cells. TCGA analysis and immunohistochemistry showed that PLCG2 was highly expressed in lung cancer tissues and tended to be associated with poor outcome. We also demonstrated that PLCG2 can promote metastasis through the regulation of mitochondrial respiration. These results suggested that PLCG2 identified by eccDNA sequencing acts as an oncogene and might be a new biomarker for NSCLC diagnosis and prognosis evaluation.

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  • Prior studies have shown contradictory findings with respect to the role of PLCG2 in proliferation and apoptosis.

    “Prior studies have shown contradictory findings with respect to the role of PLCG2 in proliferation and apoptosis.”

    From Alzheimer's disease–associated PLCG2 variants alter microglial state and function in human induced pluripotent stem cell–derived microglia‐like cells (2025) · cites this paper as [51]

    The Results section, “PLCG2 promoted the proliferation, migration, and invasion of H1299 cells” (page unavailable), says prior work implicated PLCG2 in proliferation and reports this paper’s own findings on proliferation and apoptosis. It does not describe contradictory findings from prior studies about either outcome. (LLM, conf=0.82)

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Cited by

Sorted by citations

Authors
Yang, Y., Yang, Y., Huang, H., Song, T., Mao, S., Liu, D., Zhang, L., & Li, W.
Affiliations
Sichuan University (CN)
Corresponding author
  • Liu, Dan
  • Zhang, Li
  • Li, Weimin
ORCID
Venue
Cell Death & Disease
Publisher
Springer Science and Business Media LLC
Published
2023-04-08
Volume
14
Issue
4
Pages
257-257
ISSN
2041-4889 (ISSN-L)
DOI
10.1038/s41419-023-05755-7
PMC
PMC10082821
OpenAlex
W4362720515
Cited by
41
References
2
Citations by year
2026: 8 · 2025: 18 · 2024: 13 · 2023: 2
FWCI
3.65
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Death and Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (82200078)
  • the Postdoctoral Foundation of West China Hospital, Sichuan Universit
  • the Interdisciplinary Innovation Project Fund of West China Hospital of Sichuan Universit
  • the Clinical Research Incubation Project of West China Hospital of Sichuan Universit
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
  • Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords
extrachromosomal circular DNA, PLCγ2, non-small cell lung cancer, metastasis, mitochondrial respiration, oncogenes, prognostic factors, tumor progression
MeSH terms
Carcinoma, Non-Small-Cell Lung, Cell Line, Humans, Lung Neoplasms, Respiration, RNA Interference

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