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NRSN2 promotes osteosarcoma cell proliferation and growth through PI3K/Akt/MTOR and Wnt/β-catenin signaling
Ajimu Keremu1, Xiayimaierdan Maimaiti1, Abudusaimi Aimaiti2
1Department of Micro-Reconstructive Surgery, The First Affiliated Hospital of Xinjiang Medical University No. 137 Liyushan Road, Urumqi 830054, Xinjiang, China.
Abstract:
Osteosarcoma is the most common bone cancer in children and adults. However, its pathogenesis, especially molecular mechanisms remain elusive. In current study, we screened GEO Database and found a poorly studied protein Neurensin-2 (NRSN2), which is highly expressed in osteosarcoma tissues. Neurensin-2 (NRSN2) is a small neuronal membrane protein and localized in small vesicles in neural cells, previous study found that it has been implicated in hepatocellular carcinoma (HCC) and non-small cell lung cancer (NSCLC). We here report that the expression of NRSN2 is more commonlyelevated in 18 fresh osteosarcoma tissues. Furthermore, both loss- and gain-functions assays revealed that NRSN2 could promote osteosarcoma cell proliferation and growth both in vitro and in vivo. In addition, we further found that those effects on osteosarcoma by NRSN2 are associated with the dysregulated PI3K/AKT/mTOR signaling and Wnt/β-catenin signaling. In conclusion, our study found a novel oncogenic protein, NRSN2, which promotes osteosarcoma cell proliferation and as a membrane protein, NRSN2 also could be a potential treatment target for osteosarcoma.
Insights
Neurensin-2 (NRSN2) is a novel oncogenic protein promoting osteosarcoma growth by activating key signaling pathways. This membrane protein presents a potential new therapeutic target for osteosarcoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Osteosarcoma is the most common primary bone cancer in children and adults.
- The molecular mechanisms underlying osteosarcoma pathogenesis remain largely unknown.
- Neurensin-2 (NRSN2), a neuronal membrane protein, has been implicated in other cancers like hepatocellular carcinoma and non-small cell lung cancer.
Purpose of the Study:
- To investigate the role of Neurensin-2 (NRSN2) in osteosarcoma.
- To determine if NRSN2 expression is altered in osteosarcoma tissues.
- To elucidate the functional impact and molecular mechanisms of NRSN2 in osteosarcoma progression.
Main Methods:
- Screening of the GEO Database to identify potential osteosarcoma-associated genes.
- Quantitative analysis of NRSN2 expression in osteosarcoma tissues.
- In vitro and in vivo loss- and gain-of-function assays to assess NRSN2's impact on cell proliferation and tumor growth.
- Analysis of downstream signaling pathways, including PI3K/AKT/mTOR and Wnt/β-catenin.
Main Results:
- NRSN2 expression was found to be significantly elevated in osteosarcoma tissues.
- Overexpression of NRSN2 promoted osteosarcoma cell proliferation and tumor growth both in vitro and in vivo.
- NRSN2-mediated effects were associated with the dysregulation of PI3K/AKT/mTOR and Wnt/β-catenin signaling pathways.
Conclusions:
- NRSN2 acts as a novel oncogenic protein in osteosarcoma.
- NRSN2 promotes osteosarcoma cell proliferation and growth through the PI3K/AKT/mTOR and Wnt/β-catenin signaling pathways.
- As a membrane protein, NRSN2 represents a potential therapeutic target for osteosarcoma.