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LncRNA EWSAT1 Regulates the Tumorigenesis of NSCLC as a ceRNA by Modulating miR-330-5p/ITGA5 Axis

Su Cui1, Chun-Lu Yang2, Dong-Yi Chen2

  • 1Department of Thorax, The First Affiliated Hospital of China Medical University, No. 155, Nanjing North Street, Heping District, Shenyang, Liaoning, 110001, People's Republic of China. cuisu@126.com.

Biochemical Genetics
|April 30, 2021
PubMed

Insights

Long non-coding RNA EWSAT1 promotes non-small cell lung cancer (NSCLC) tumorigenesis by sponging miR-330-5p to upregulate ITGA5. Silencing EWSAT1 inhibits NSCLC progression and tumor growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality.
  • The molecular mechanisms underlying NSCLC tumorigenesis require further elucidation.
  • Long non-coding RNAs (lncRNAs) are emerging as critical regulators in various cancers.

Purpose of the Study:

  • To investigate the role of lncRNA EWSAT1 in NSCLC tumorigenesis.
  • To explore the regulatory axis involving EWSAT1, miR-330-5p, and ITGA5 in NSCLC.
  • To determine the therapeutic potential of targeting EWSAT1 in NSCLC.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) to assess EWSAT1 expression in NSCLC tissues.
  • In vitro assays (cell proliferation, apoptosis, invasion, migration) in A549 cells with various genetic manipulations (shEWSAT1, miR-330-5p inhibitor, siITGA5).
  • Dual luciferase reporter gene assay to confirm targeting relationships.
  • In vivo xenograft models in nude mice to evaluate tumor growth and associated molecular changes.

Main Results:

  • EWSAT1 was significantly upregulated in NSCLC tissues and correlated with clinical parameters.
  • Silencing EWSAT1 inhibited NSCLC cell proliferation, invasion, and migration while promoting apoptosis.
  • EWSAT1 acts as a competing endogenous RNA (ceRNA) by sponging miR-330-5p, leading to increased ITGA5 expression.
  • Inhibition of EWSAT1 suppressed tumor growth in vivo, reducing Ki67 expression and increasing apoptosis.

Conclusions:

  • lncRNA EWSAT1 plays a crucial oncogenic role in NSCLC progression.
  • The EWSAT1/miR-330-5p/ITGA5 axis is a key regulatory pathway in NSCLC tumorigenesis.
  • Targeting EWSAT1 represents a potential therapeutic strategy for NSCLC.
Keywords:
EWSAT1ITGA5Non-small cell lung cancermiR-330-5p

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