Osthole Inhibits Breast Cancer Progression through Upregulating Tumor Suppressor GNG7

Area of Science:

• Oncology
• Pharmacology
• Bioinformatics

Background:

• Osthole (OST) is a plant-derived compound with demonstrated tumor-suppressive properties across various cancers.
• The precise mechanisms underlying OST's inhibitory effects on breast cancer (BrCa) remain largely unelucidated.
• Understanding OST's molecular targets is crucial for developing novel BrCa therapeutics.

Purpose of the Study:

• To identify potential molecular targets of Osthole (OST) in breast cancer (BrCa) using bioinformatics analysis.
• To investigate the role of GNG7 in BrCa and its relationship with OST.
• To validate GNG7 as a potential therapeutic target for OST in BrCa treatment.

Main Methods:

• Utilized the GSE85871 dataset for comprehensive bioinformatics analysis to identify OST targets in BrCa.
• Conducted a series of in vitro experiments to assess GNG7 expression, function, and its interaction with OST in BrCa cells.
• Employed gene silencing and overexpression techniques to evaluate the functional impact of GNG7 on BrCa cell behavior.

Main Results:

• GNG7 was identified as a key target of OST, showing significant upregulation upon OST exposure in BrCa cells.
• GNG7 expression was found to be downregulated in BrCa tissues compared to normal tissues, correlating with poorer patient survival (OS and RFS).
• GNG7 silencing promoted BrCa cell proliferation and inhibited apoptosis, while GNG7 overexpression reversed these effects. Crucially, GNG7 inhibition counteracted OST's cytotoxic effects.

Conclusions:

• GNG7 is identified as a novel, OST-dependent therapeutic target in breast cancer.
• GNG7 functions as a tumor suppressor in BrCa, with its downregulation associated with adverse clinical outcomes.
• Osthole demonstrates therapeutic potential for BrCa via a mechanism dependent on GNG7 upregulation.