Targeting the lncRNA RBM5-AS1/GCN5 axis under fasting conditions reprograms Glycolysis and induces apoptosis in

Gayathiri Gunasangkaran1, Saradhadevi Muthukrishnan2, Anjali K Ravi1

  • 1Department of Biochemistry, Bharathiar University, Coimbatore, Tamilnadu, India.

PubMed
Abstract

Insights

Fasting enhances RBM5-AS1 knockdown and GCN5 inhibition, significantly reducing ovarian cancer cell viability and promoting apoptosis. This metabolic and epigenetic strategy offers a promising new avenue for ovarian cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Metabolic Research

Background:

  • Ovarian cancer is a complex malignancy influenced by long non-coding RNAs (lncRNAs).
  • RBM5-AS1, a lncRNA, interacts with GCN5 to acetylate PGC-1α, promoting the Warburg effect in cancer.
  • The impact of fasting on the RBM5-AS1/GCN5 axis in ovarian cancer is not well understood.

Purpose of the Study:

  • To evaluate the therapeutic efficacy of RBM5-AS1 knockdown and GCN5 inhibition under fasting-mimicked conditions.
  • To investigate the combined effects on ovarian cancer cell lines (SKOV3).

Main Methods:

  • Utilized cytotoxicity assays, LDH assays, migration assays, and apoptosis staining (DAPI, acridine orange/ethidium bromide).
  • Performed flow cytometry for cell death analysis.
  • Conducted gene expression analysis of Warburg effect-related genes and apoptotic markers.

Main Results:

  • The combination of fasting, RBM5-AS1 knockdown (siRNA), and GCN5 inhibition (MB-3) demonstrated the most potent anticancer effect.
  • This combination significantly reduced cell viability, induced membrane damage, inhibited migration and colony formation, and promoted apoptosis (>80% late apoptotic/necrotic cells).
  • Observed downregulation of Warburg genes and upregulation of PDH and pro-apoptotic markers, with reduced PGC-1α acetylation.

Conclusions:

  • Fasting potentiates the therapeutic effects of RBM5-AS1 knockdown and GCN5 inhibition in ovarian cancer.
  • This combinatorial approach disrupts glycolytic metabolism and promotes apoptosis, representing a promising metabolic and epigenetic strategy.

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