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The tumor suppressor role of PAQR3 in osteosarcoma
Zhiqiang Ma1, Yanlong Wang, Taikui Piao
1Department of Orthopedic Surgery, The Second Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150086, People's Republic of China.
Abstract:
Osteosarcoma is the most common primary bone malignancy; however, the molecular mechanisms of development are not well understood. Progestin and AdipoQ receptors (PAQR3), a protein specifically localized in the Golgi apparatus, was recently characterized as a new tumor suppressor. Little is known about the expression and function of PAQR3 in osteosarcoma. Here, we showed that PAQR3 was downregulated in osteosarcoma tissues compared with the adjacent normal regions in 80 paired samples. Moreover, lower levels of PAQR3 were associated with metastasis in clinical osteosarcoma patients. In addition, overexpression of PAQR3 in the osteosarcoma cell line MG-63 inhibited cell proliferation, migration, and invasion by promoting ERK phosphorylation. Taken together, our results indicated that PAQR3 might act as a tumor suppressor in osteosarcoma, providing a novel diagnostic and therapeutic option for human osteosarcoma in the future.
Insights
Progestin and AdipoQ receptors (PAQR3) is downregulated in osteosarcoma, correlating with metastasis. Overexpressing PAQR3 inhibits cancer cell growth, suggesting its role as a tumor suppressor for potential osteosarcoma therapies.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Osteosarcoma is the most common primary bone cancer, with poorly understood molecular drivers.
- Progestin and AdipoQ receptors (PAQR3) is a Golgi-localized protein recently identified as a tumor suppressor.
- The role of PAQR3 in osteosarcoma pathogenesis remains largely unexplored.
Purpose of the Study:
- To investigate the expression levels of PAQR3 in osteosarcoma tissues.
- To determine the correlation between PAQR3 expression and clinicopathological features, including metastasis.
- To elucidate the functional role of PAQR3 in osteosarcoma cell behavior and its underlying molecular mechanisms.
Main Methods:
- PAQR3 expression was quantified in 80 paired osteosarcoma and adjacent normal tissues.
- Correlation analysis was performed between PAQR3 levels and clinical data, focusing on metastasis.
- Functional assays (proliferation, migration, invasion) were conducted in osteosarcoma cells (MG-63) with PAQR3 overexpression, assessing ERK phosphorylation.
Main Results:
- PAQR3 expression was significantly downregulated in osteosarcoma tissues compared to normal adjacent tissues.
- Lower PAQR3 levels were associated with increased metastasis in osteosarcoma patients.
- Overexpression of PAQR3 suppressed osteosarcoma cell proliferation, migration, and invasion, mediated by enhanced ERK phosphorylation.
Conclusions:
- PAQR3 functions as a tumor suppressor in osteosarcoma.
- Downregulation of PAQR3 is linked to disease progression and metastasis.
- PAQR3 represents a potential diagnostic marker and therapeutic target for osteosarcoma.
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