Targeting G9a Exerts Pleiotropic Suppression in Triple-Negative Breast Cancer Cells: Cooperatively Inducing...

Area of Science:

• Oncology
• Cell Biology
• Molecular Biology

Background:

• Pyroptosis, a pro-inflammatory programmed cell death, is crucial in tumor biology, particularly in triple-negative breast cancer (TNBC).
• G9a inhibition shows anticancer potential, but its precise molecular mechanisms in TNBC remain largely unelucidated.
• Understanding these mechanisms is vital for developing novel therapeutic strategies against TNBC.

Purpose of the Study:

• To investigate whether G9a inhibition suppresses TNBC progression by promoting pyroptosis.
• To elucidate the molecular pathways involved in G9a inhibition-induced pyroptosis in TNBC cells.

Main Methods:

• Utilized TNBC cell lines (MDA-MB-231, SUM159PT) and a normal cell line (MCF-10A) for in vitro studies.
• Assessed cell proliferation, death, invasion, and migration using CCK8, EdU, flow cytometry, and transwell assays.
• Analyzed inflammatory factors, gene/protein expression (RIG-I, STAT1, GSDME), and cellular morphology via ELISA, qRT-PCR, Western blot, immunofluorescence, and transmission electron microscopy.

Main Results:

• G9a knockdown significantly inhibited TNBC cell growth, invasion, and migration.
• G9a inhibition induced pyroptosis and upregulated RIG-I, p-STAT1, and GSDME expression in TNBC cells.
• RIG-I inhibition partially reversed the pyroptosis induced by G9a knockdown, confirming the pathway's role.

Conclusions:

• G9a inhibition triggers pyroptosis in TNBC cells via the RIG-I/STAT1/GSDME signaling pathway.
• This pathway presents a novel therapeutic target for treating triple-negative breast cancer.
• Targeting G9a offers a promising strategy for enhancing anti-TNBC treatment efficacy.