MARCH6 promotes Papillary Thyroid Cancer development by destabilizing DHX9

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Membrane-associated ring-CH-type finger (MARCH) proteins are E3 ubiquitin ligases impacting protein stability.
• Some MARCH proteins are implicated in cancer development, but MARCH6's role in thyroid tumorigenesis is uncharacterized.

Purpose of the Study:

• To investigate the role of MARCH6 in thyroid cancer development.
• To elucidate the molecular mechanisms underlying MARCH6's function in thyroid tumorigenesis.

Main Methods:

• Quantitative analysis of MARCH6 mRNA and protein levels in papillary thyroid cancer (PTC) tissues.
• In vitro gain-of-function and loss-of-function studies in thyroid cancer cell lines.
• Co-immunoprecipitation assays to identify MARCH6 interacting partners.
• Western blotting to assess protein levels and signaling pathway activation (AKT/mTOR).

Main Results:

• MARCH6 expression was significantly upregulated in the majority of primary PTCs at both mRNA and protein levels.
• MARCH6 overexpression promoted cell proliferation, migration, and tumorigenesis while suppressing apoptosis in thyroid cancer cells.
• MARCH6 directly interacted with and downregulated DHX9, a protein that enhances proliferation and migration.
• MARCH6 activated the AKT/mTOR signaling pathway, dependent on DHX9 downregulation.

Conclusions:

• MARCH6 acts as a potential oncogene in thyroid cancer.
• MARCH6 promotes thyroid cancer progression by destabilizing DHX9 and activating the AKT/mTOR pathway.