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LncRNA WT1-AS Inhibits Triple-Negative Breast Cancer Cell Migration and Invasion by Downregulating Transforming
Jiangfen Wang1, Chunfang Xi1, Xuan Yang1
1Department of General Surgery, Shanxi Provincial People's Hospital, Taiyuan City, P.R. China.
Abstract:
Long noncoding RNA WT1-AS has been demonstrated as a potential tumor suppressor in gastric cancer. However, the functions of WT1-AS in other types of cancer remain unclear. Our study was therefore performed to explore the role of WT1-AS in triple-negative breast cancer (TNBC). Tissue specimens were obtained from 62 TNBC patients included in this study. A TNBC cell line BT-549 was used as the cell model of TNBC. Gene expression was detected by qPCR and Western blot. Overexpression experiments were used to analyze gene interactions. Transwell assays were used to explore the effects of transfections on cell invasion and migration. We found that WT1-AS was downregulated in TNBC tissues than in nontumor tissues and decreased with increase in clinical stages. Transforming growth factor β1 (TGF-β1) was upregulated in TNBC tissues and inversely correlated with WT1-AS. TGF-β1 overexpression did not significantly affect WT1-AS in BT-549 cells, but WT1-AS negatively regulated the expression of TGF-β1. WT1-AS overexpression caused inhibited migration and invasion of TNBC cells. TGF-β1 overexpression showed opposite functions and reduced the effects of WT1-AS overexpression. WT1-AS may downregulate TGF-β to inhibit the migration and invasion of TNBC cells.
Insights
Long noncoding RNA WT1-AS acts as a tumor suppressor in triple-negative breast cancer (TNBC). It downregulates transforming growth factor β1 (TGF-β1), inhibiting TNBC cell migration and invasion.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Long noncoding RNA WT1-AS is a potential tumor suppressor in gastric cancer.
- The role of WT1-AS in other cancers, including triple-negative breast cancer (TNBC), is not well understood.
Purpose of the Study:
- To investigate the function of WT1-AS in triple-negative breast cancer (TNBC).
- To explore the relationship between WT1-AS and transforming growth factor β1 (TGF-β1) in TNBC.
Main Methods:
- Gene expression analysis (qPCR, Western blot) in 62 TNBC patient tissues and BT-549 cell line.
- Overexpression experiments to analyze gene interactions and regulatory effects.
- Transwell assays to assess the impact of WT1-AS and TGF-β1 on cell invasion and migration.
Main Results:
- WT1-AS expression was downregulated in TNBC tissues and correlated with advanced clinical stages.
- Transforming growth factor β1 (TGF-β1) was upregulated in TNBC tissues and inversely correlated with WT1-AS.
- WT1-AS overexpression inhibited TNBC cell migration and invasion, while TGF-β1 overexpression reversed these effects.
- WT1-AS was found to negatively regulate TGF-β1 expression.
Conclusions:
- WT1-AS functions as a tumor suppressor in TNBC by downregulating TGF-β1.
- Inhibition of TNBC cell migration and invasion by WT1-AS is mediated through the TGF-β1 pathway.
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