NBAT1 suppresses breast cancer metastasis by regulating DKK1 via PRC2
Pengnan Hu1,2,3, Junjun Chu1,3, Yanqing Wu1,3
1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Abstract:
Long noncoding RNA NBAT1 (neuroblastoma associated transcript 1) regulates cell proliferation and invasion by interacting with PRC2 (polycomb repressive complex 2) member EZH2 (enhancer of zeste 2). Decreased expression of NBAT1 is associated with poor clinical outcome in neuroblastomas. However, the roles of NBAT1 in other cancers remain unknown. Here, we report that NBAT1 is down-regulated in various types of cancer. Particularly, reduced NBAT1 in breast cancer is associated with tumor metastasis and poor patient prognosis. In vitro, ectopic NBAT1 inhibits migration and invasion of breast cancer cells. Mechanistic study shows that NBAT1 is associated with PRC2 member EZH2 and regulates global gene expression profile. Among them, DKK1 (dickkopf WNT signaling pathway inhibitor 1) is found to be regulated by NBAT1 in a PRC2 dependent manner, and is responsible for NBAT1's effects in inhibiting migration and invasion of breast cancer cells. Taken together, our study demonstrates that long noncoding RNA NBAT1 is a potential breast cancer prognostic marker, as well as a potential therapeutic target to inhibit breast cancer metastasis.
Insights
Long noncoding RNA NBAT1 (neuroblastoma associated transcript 1) is down-regulated in breast cancer, correlating with metastasis and poor prognosis. Restoring NBAT1 inhibits cancer cell invasion, suggesting it as a therapeutic target.
Area of Science:
- Molecular oncology
- Cancer epigenetics
- Noncoding RNA biology
Background:
- Long noncoding RNA NBAT1 (neuroblastoma associated transcript 1) is known to regulate proliferation and invasion via EZH2 interaction.
- Reduced NBAT1 expression is linked to poor outcomes in neuroblastomas.
- The function of NBAT1 in other cancer types, including breast cancer, is largely unexplored.
Purpose of the Study:
- To investigate the role of NBAT1 in various cancers, with a specific focus on breast cancer.
- To determine the association between NBAT1 expression and breast cancer progression, metastasis, and patient prognosis.
- To elucidate the molecular mechanisms underlying NBAT1's function in breast cancer.
Main Methods:
- Analysis of NBAT1 expression levels across different cancer types.
- In vitro experiments to assess the impact of ectopic NBAT1 expression on breast cancer cell migration and invasion.
- Mechanistic studies involving interaction analysis with PRC2 member EZH2 and gene expression profiling.
- Investigation of downstream targets, such as DKK1, regulated by NBAT1.
Main Results:
- NBAT1 is down-regulated in multiple cancer types, including breast cancer.
- Reduced NBAT1 levels in breast cancer correlate significantly with tumor metastasis and unfavorable patient prognosis.
- Overexpression of NBAT1 in vitro suppresses breast cancer cell migration and invasion.
- NBAT1 interacts with EZH2 and influences global gene expression, with DKK1 identified as a key downstream mediator responsible for NBAT1's anti-metastatic effects.
Conclusions:
- Long noncoding RNA NBAT1 functions as a tumor suppressor in breast cancer.
- NBAT1 serves as a potential prognostic biomarker for breast cancer.
- Targeting NBAT1 represents a promising therapeutic strategy to inhibit breast cancer metastasis.
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