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LncRNA MACC1-AS1 facilitates the cell growth of small cell lung cancer by sequestering miR-579-3p and mediating

Jiang Hong1, Rentong Gu2, Wen Cheng1

  • 1Department of Thoracic Surgery, Changhai Hospital, Naval Medical University, Shanghai 200433, China.

International Journal of Biological Macromolecules
|October 14, 2024
PubMed

Insights

Long non-coding RNA MACC1-AS1 promotes small cell lung cancer (SCLC) growth by interacting with miR-579-3p and activating the NOTCH1 pathway. Inhibiting MACC1-AS1 suppressed cancer progression and induced apoptosis in SCLC cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • Long non-coding RNAs (lncRNAs) play critical roles in disease progression, particularly in cancers.
  • The specific function and mechanism of lncRNA MACC1 antisense RNA 1 (MACC1-AS1) in small cell lung cancer (SCLC) remain largely unelucidated.

Purpose of the Study:

  • To investigate the biological role and underlying molecular mechanism of MACC1-AS1 in the progression of SCLC.
  • To determine the relationship between MACC1-AS1, miR-579-3p, and the NOTCH1 pathway in SCLC.

Main Methods:

  • Quantitative real-time PCR to measure MACC1-AS1 levels in SCLC cells.
  • Cell proliferation, migration, and apoptosis assays following MACC1-AS1 knockdown.
  • Western blotting to assess NOTCH pathway gene expression.
  • MiRNA target prediction and validation assays.
  • Rescue experiments involving miR-579-3p inhibition and NOTCH1 overexpression.

Main Results:

  • MACC1-AS1 expression was significantly upregulated in SCLC cells.
  • MACC1-AS1 knockdown inhibited SCLC cell proliferation and migration while inducing apoptosis.
  • MACC1-AS1 knockdown suppressed NOTCH pathway activation, an effect reversed by Jagged1.
  • NOTCH1 deficiency impaired SCLC cell growth.
  • MACC1-AS1 was found to sequester miR-579-3p, which targets NOTCH1.
  • miR-579-3p inhibition or NOTCH1 overexpression rescued the suppressive effects of MACC1-AS1 knockdown on SCLC cell growth.

Conclusions:

  • lncRNA MACC1-AS1 promotes SCLC cell growth and progression.
  • MACC1-AS1 exerts its oncogenic function by sponging miR-579-3p, leading to NOTCH1 pathway activation.
  • Targeting MACC1-AS1 represents a potential therapeutic strategy for SCLC.
Keywords:
MACC1-AS1NOTCH1Small cell lung cancermiR-579-3p

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