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Long noncoding RNA HAS2-AS1 accelerates non-small cell lung cancer chemotherapy resistance by targeting LSD1/EphB3

Peng Sun1, Limin Sun1, Jia Cui1

  • 1Department of Oncology, The Second Hospital of Dalian Medical University Dalian, China.

American Journal of Translational Research
|April 10, 2020
PubMed

Insights

Long noncoding RNA hyaluronan synthase 2 antisense 1 (HAS2-AS1) promotes non-small cell lung cancer (NSCLC) growth and chemoresistance. Targeting HAS2-AS1 offers a potential therapeutic strategy for NSCLC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Long noncoding RNAs (lncRNAs) play critical roles in various cancers, including non-small cell lung cancer (NSCLC).
  • The specific involvement of lncRNA hyaluronan synthase 2 antisense 1 (HAS2-AS1) in NSCLC tumorigenesis remains largely uncharacterized.

Purpose of the Study:

  • To investigate the role and underlying mechanism of HAS2-AS1 in the development and progression of NSCLC.
  • To determine the prognostic significance of HAS2-AS1 in NSCLC patients.

Main Methods:

  • Analysis of HAS2-AS1 expression levels in NSCLC tissues and adjacent normal tissues.
  • In vitro functional assays (proliferation, invasion) and chemoresistance studies in NSCLC cell lines with HAS2-AS1 manipulation.
  • In vivo tumor xenograft models to assess the effect of HAS2-AS1 knockdown on tumor growth.
  • Mechanistic studies involving chromatin immunoprecipitation (ChIP) to examine the interaction of HAS2-AS1 with lysine-specific demethylase 1 (LSD1) and the EphB3 promoter.

Main Results:

  • HAS2-AS1 was significantly upregulated in NSCLC tissues and correlated with poor patient prognosis.
  • Overexpression of HAS2-AS1 promoted NSCLC cell proliferation, invasion, and resistance to gefitinib chemotherapy.
  • Knockdown of HAS2-AS1 inhibited tumor growth in vivo.
  • Mechanistically, HAS2-AS1 was found to recruit LSD1 to the EphB3 promoter, leading to the inhibition of EphB3 transcription.

Conclusions:

  • HAS2-AS1 acts as a crucial oncogenic lncRNA in NSCLC tumorigenesis.
  • HAS2-AS1 promotes NSCLC progression by inhibiting EphB3 transcription via LSD1 recruitment.
  • HAS2-AS1 represents a potential therapeutic target for NSCLC treatment.
Keywords:
EphB3HAS2-AS1LSD1Non-small cell lung cancer

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