YO2 Induces Melanoma Cell Apoptosis through p53-Mediated LRP1 Downregulation

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Low-density lipoprotein receptor-related protein 1 (LRP1) is implicated in melanoma progression.
• The mechanism of LRP1 regulation in melanoma remains unclear.
• TP53, a tumor suppressor, is often retained but inactive in melanoma.

Purpose of the Study:

• To investigate the role of TP53 in regulating LRP1 expression and melanoma growth.
• To identify novel therapeutic strategies targeting LRP1 and TP53 pathways in melanoma.

Main Methods:

• TP53 overexpression via lentivirus or YO-2 treatment in human and murine melanoma cells.
• Quantification of miR-103/107 and LRP1 expression.
• In vitro and in vivo assessment of melanoma cell proliferation and tumor growth.
• Evaluation of YO-2 as a TP53 inducer and its combination therapy with doxorubicin.

Main Results:

• TP53 restoration increased miR-103/107 expression, leading to LRP1 downregulation.
• LRP1 downregulation and TP53 restoration suppressed melanoma growth in vitro and in vivo.
• YO-2 treatment induced TP53, suppressed melanoma growth, and enhanced miR-103/107 expression.
• LRP1 overexpression or p53 downregulation counteracted YO-2's anti-melanoma effects.
• YO-2 combined with doxorubicin effectively inhibited tumor growth in a murine model.

Conclusions:

• TP53 acts as a regulator of LRP1-mediated melanoma growth through miR-103/107.
• The small molecule YO-2 is a novel TP53 inducer with anti-melanoma activity.
• YO-2 shows potential as a therapeutic agent for melanoma, alone or in combination therapy.