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Silencing lnc-ASAH2B-2 Inhibits Breast Cancer Cell Growth via the mTOR Pathway

Jingjing Li1,2, Jing Zhang1,3, Liang Jin1,2

  • 1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, P.R. China.

Anticancer Research
|June 1, 2018
PubMed
Abstract

Insights

Everolimus resistance in breast cancer may involve the long noncoding RNA lnc-ASAH2B-2. Reducing this RNA inhibits cancer cell growth, suggesting it as a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Persistent activation of the PI3K/Akt/mTOR pathway drives breast cancer resistance to endocrine therapy.
  • Everolimus inhibits mTOR but shows limited single-agent clinical activity.
  • The role of long noncoding RNAs (lncRNAs) in everolimus resistance is currently unknown.

Purpose of the Study:

  • To investigate the involvement of lncRNA N-acylsphingosine amidohydrolase 2B-2 (lnc-ASAH2B-2) in everolimus resistance in breast cancer.
  • To determine if lnc-ASAH2B-2 modulates breast cancer cell proliferation and the mTOR pathway.

Main Methods:

  • Knockdown of lnc-ASAH2B-2 was performed in BT474 and MCF7 breast cancer cell lines.
  • Cell viability, colony formation, and proliferation assays were utilized to assess the functional impact of lnc-ASAH2B-2 reduction.

Main Results:

  • Everolimus treatment led to the upregulation of lnc-ASAH2B-2 in both serum-containing and serum-free conditions.
  • Decreased expression of lnc-ASAH2B-2 effectively inhibited the proliferation of BT474 and MCF7 breast cancer cells.

Conclusions:

  • lnc-ASAH2B-2 is upregulated following everolimus exposure in breast cancer cells.
  • lnc-ASAH2B-2 activation of the mTOR pathway contributes to breast cancer cell growth and may diminish everolimus efficacy.
  • lnc-ASAH2B-2 represents a potential novel therapeutic target for overcoming everolimus resistance in breast cancer.
Keywords:
Breast cancereverolimuslnc-ASAH2B-2long noncoding RNAtherapeutic target

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