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Silencing lncRNA-DARS-AS1 suppresses nonsmall cell lung cancer progression by stimulating miR-302a-3p to inhibit

Ji Li1, Yizhuo Li1, Xiaodan Sun2

  • 1Department of Pathology, The First Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.

Molecular Carcinogenesis
|January 30, 2024
PubMed

Insights

Long noncoding RNA DARS-AS1 promotes nonsmall cell lung cancer (NSCLC) by interacting with miR-302a-3p to regulate ACAT1. Targeting this pathway may offer new therapeutic strategies for NSCLC patients.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Long noncoding RNAs (LncRNAs) are increasingly recognized as critical regulators in cancer development.
  • Nonsmall cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide.
  • Identifying novel molecular targets is crucial for advancing NSCLC therapeutics.

Purpose of the Study:

  • To investigate the role of lncRNA DARS-AS1, miR-302a-3p, and ACAT1 in NSCLC.
  • To elucidate the molecular mechanisms underlying the DARS-AS1-mediated regulation of NSCLC progression.
  • To explore the potential of the DARS-AS1-miR-302a-3p-ACAT1 axis as a therapeutic target.

Main Methods:

  • Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for transcript analysis.
  • Western blotting to assess protein expression and pathway activation (AKT/ERK).
  • Cellular assays (MTS, Transwell, apoptosis), Fluorescence in situ hybridization (FISH), dual-luciferase reporter assays, RNA immunoprecipitation, and in vivo xenograft models.

Main Results:

  • lncRNA DARS-AS1 was significantly upregulated in NSCLC tissues and cell lines, correlating with poorer patient survival.
  • Knockdown of DARS-AS1 suppressed NSCLC cell proliferation, migration, and invasion, while promoting apoptosis.
  • DARS-AS1 exerted its oncogenic effects by sponging miR-302a-3p, leading to the upregulation of its target, the oncogene ACAT1, and activating the AKT/ERK signaling pathway.

Conclusions:

  • The DARS-AS1/miR-302a-3p/ACAT1 axis is a critical regulator of NSCLC pathogenesis.
  • DARS-AS1 functions as an oncogenic lncRNA in NSCLC by modulating the miR-302a-3p/ACAT1 interaction.
  • Targeting the DARS-AS1-miR-302a-3p-ACAT1 pathway presents a promising therapeutic strategy for NSCLC.
Keywords:
ACAT1AKT/ERK pathwayDARS-AS1competing endogenous RNAlung cancer

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