SUMO-specific protease 2 (SENP2) functions as a tumor suppressor in osteosarcoma via SOX9 degradation

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Osteosarcoma (OS) is a prevalent pediatric bone cancer with unknown pathogenesis.
• Small ubiquitin-like modifier (SUMO)-Specific Protease 2 (SENP2) functions as a tumor suppressor in other cancers.
• The role of SENP2 in OS requires further investigation.

Purpose of the Study:

• To elucidate the function of SENP2 in osteosarcoma.
• To determine the downstream targets and mechanisms of SENP2 in OS.

Main Methods:

• Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assays were used to assess SENP2 expression.
• CRISPR-Cas9 gene editing was employed for SENP2 knockdown.
• Cell proliferation, migration, and invasion assays were performed.
• Ubiquitination and degradation assays were conducted to study the interaction between SENP2 and SOX9.

Main Results:

• SENP2 expression was significantly downregulated in clinical OS tissues.
• SENP2 overexpression suppressed OS cell proliferation, migration, and invasion.
• SENP2 knockdown accelerated OS cell growth and migration.
• SENP2 promotes proteasome-dependent ubiquitination and degradation of SRY-box-9 (SOX9).
• SOX9 silencing counteracted the effects of SENP2 depletion on cell growth and migration.

Conclusions:

• SENP2 acts as a tumor suppressor in osteosarcoma.
• SENP2 inhibits OS progression by targeting SOX9 for degradation.
• SOX9 is a critical downstream effector of SENP2 in osteosarcoma pathogenesis.