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Long noncoding RNA LHFPL3-AS2 suppresses metastasis of non-small cell lung cancer by interacting with SFPQ to

Zhuoan Cheng1, Chunlai Lu2, Hui Wang1

  • 1State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China.

Cancer Letters
|February 1, 2022
PubMed

Insights

This study identifies LHFPL3-AS2 as a novel long noncoding RNA (lncRNA) significantly decreased in non-small cell lung cancer (NSCLC). Lower LHFPL3-AS2 levels correlate with poor prognosis and promote NSCLC cell invasion and metastasis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Lung cancer is a leading cause of cancer mortality globally.
  • The role of long noncoding RNAs (lncRNAs) in non-small cell lung cancer (NSCLC) pathogenesis is not fully understood.
  • Identifying novel molecular markers and therapeutic targets is crucial for improving NSCLC outcomes.

Purpose of the Study:

  • To investigate the expression profile and functional role of lncRNAs in NSCLC.
  • To identify novel lncRNAs associated with NSCLC progression and patient survival.
  • To elucidate the molecular mechanism underlying the function of a newly identified lncRNA in NSCLC.

Main Methods:

  • Genome-wide lncRNA expression profiling using Affymetrix Gene Chip Human Transcriptome Array 2.0 in 37 paired NSCLC tissues and adjacent nontumorous tissues.
  • Validation of lncRNA expression in an additional 93 paired NSCLC samples.
  • In vitro and in vivo assays to assess the functional impact of LHFPL3-AS2 on NSCLC cell invasion and metastasis.
  • Mechanistic studies involving RNA-protein interactions, promoter binding assays, and gene expression analysis.

Main Results:

  • A novel lncRNA, LHFPL3-AS2, was identified and found to be significantly downregulated in NSCLC tissues.
  • Low LHFPL3-AS2 expression levels were strongly correlated with advanced TNM stage, metastasis, and poor overall survival in NSCLC patients.
  • Overexpression of LHFPL3-AS2 suppressed NSCLC cell invasion and metastasis both in vitro and in vivo.
  • Downregulation of LHFPL3-AS2 led to reduced interaction with SFPQ, increased SFPQ binding to the TXNIP promoter, and subsequent transcriptional repression of TXNIP, promoting NSCLC cell migration and invasion.
  • LHFPL3-AS2 expression was regulated by EGR1 under hypoxic conditions.

Conclusions:

  • LHFPL3-AS2 is a novel tumor suppressor lncRNA in NSCLC, with its downregulation contributing to tumor progression.
  • LHFPL3-AS2 exerts its tumor-suppressive function by modulating the SFPQ-TXNIP axis.
  • LHFPL3-AS2 may serve as a potential prognostic biomarker and therapeutic target for NSCLC.
Keywords:
Long noncoding RNAMetastasisNon-small cell lung cancerThioredoxin interacting proteinTumor suppressor gene

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