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Long noncoding RNA NBAT1 negatively modulates growth and metastasis of osteosarcoma cells through suppression of
Cheng Yang1, Guijiang Wang1, Jian Yang1
1No.4 Department of Orthopedics, Cangzhou Central HospitalCangzhou 061001, Hebei Province, China.
Abstract:
Osteosarcoma (OS) is the most common primary bone malignancies. Long noncoding RNAs (lncRNAs) are key regulatory RNAs which takes part in several biological processes. LncRNA neuroblastoma associated transcript 1 (NBAT1) is a newly identified functional lncRNA. NBAT1 functions as a tumor suppressor in some cancers. However, the expression pattern, the biological function and the mechanisms of NBAT1 in OS progress have not been elucidated. In this study, for the first time, we found that NBAT1 expression is downregulated in OS tissues and cell lines and is associated with clinical stage, distant metastasis and poor prognosis. Loss- and gain-of-function assays showed that NBAT1 played a negative regulatory role in OS growth and metastasis in vitro and in vivo. Further investigation demonstrated that NBAT1 physically interacted with miR-21 and then suppressed its expression. NBAT1 also regulated downstream genes targeted by miR-21, including PTEN, PDCD4, TPM1 and RECK. These findings may extend the function of NBAT1 in tumor progression and provide a novel target for OS treatment.
Insights
Long noncoding RNA NBAT1 is downregulated in osteosarcoma (OS) and suppresses tumor growth and metastasis. NBAT1 interacts with miR-21, offering a potential new therapeutic target for this common bone cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Osteosarcoma (OS) is the most common primary bone cancer.
- Long noncoding RNAs (lncRNAs) are crucial regulators in biological processes.
- NBAT1, a lncRNA, acts as a tumor suppressor in some cancers, but its role in OS is unclear.
Purpose of the Study:
- To investigate the expression, function, and mechanism of lncRNA NBAT1 in osteosarcoma.
- To determine if NBAT1 acts as a tumor suppressor in OS.
- To explore NBAT1's interaction with microRNAs in OS progression.
Main Methods:
- Analysis of NBAT1 expression in OS tissues and cell lines.
- Loss- and gain-of-function assays (in vitro and in vivo) to assess NBAT1's role in OS growth and metastasis.
- Investigation of NBAT1's interaction with miR-21 and its downstream targets.
Main Results:
- NBAT1 expression is significantly downregulated in OS tissues and cell lines.
- Downregulated NBAT1 correlates with advanced clinical stage, distant metastasis, and poor prognosis.
- NBAT1 inhibits OS cell growth and metastasis by suppressing miR-21 and its downstream targets (PTEN, PDCD4, TPM1, RECK).
Conclusions:
- NBAT1 functions as a tumor suppressor in osteosarcoma.
- NBAT1 inhibits OS progression by regulating the miR-21 pathway.
- NBAT1 represents a potential novel therapeutic target for osteosarcoma treatment.
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