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3-D Cell Culture System for Studying Invasion and Evaluating Therapeutics in Bladder Cancer
Published on: September 13, 2018
Long Noncoding RNA ATB Promotes Proliferation, Migration, and Invasion in Bladder Cancer by Suppressing MicroRNA-126
1Department of Urology, Zoucheng People's Hospital, Zoucheng, Shandong, P.R. China.
Abstract:
This study aimed to explore the biological functions of long noncoding RNA activated by transforming growth factor-β (lncRNA-ATB) in bladder cancer cells. For the expressions of lncRNA-ATB, miR-126, and KRAS, T24 cells were transfected with their specific vectors/shRNA or mimic/inhibitor. Then cell viability, migration, invasion, and apoptosis as well as the protein levels of apoptosis-related factors and PI3K/AKT and mTOR signal pathways were measured. The relationships of lncRNA-ATB and miR-126 or miR-126 and KRAS were analyzed by Dual-Luciferase Reporter assay. Functional experiments showed that lncRNA-ATB overexpression significantly promoted cell viability, migration, and invasion in T24 cells. lncRNA-ATB was a molecular sponge of miR-126 and exerted tumor-promoting effects by downregulation of miR-126. Moreover, KRAS was a direct target of miR-126 and was negatively regulated by miR-126. Finally, overexpression of KRAS increased cell viability, migration, and invasion, as well as activated PI3K/AKT and mTOR signaling pathways in T24 cells. The results revealed that lncRNA-ATB was an oncogene, which promoted cell proliferation, migration, and invasion by regulating miR-126 in bladder cancer. These findings may provide a potential prognostic biomarker and a therapeutic target for bladder cancer.
Insights
Long noncoding RNA activated by TGF-β (lncRNA-ATB) promotes bladder cancer progression by downregulating miR-126 and upregulating KRAS. This suggests lncRNA-ATB is a potential therapeutic target for bladder cancer.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Bladder cancer remains a significant health concern with limited therapeutic options.
- Long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in cancer development.
- The specific functions of lncRNA-ATB in bladder cancer are not fully understood.
Purpose of the Study:
- To investigate the biological functions of lncRNA-ATB in bladder cancer cells.
- To elucidate the molecular mechanisms underlying lncRNA-ATB's role in bladder cancer.
- To assess the potential of lncRNA-ATB as a prognostic biomarker and therapeutic target.
Main Methods:
- T24 bladder cancer cells were transfected with vectors/shRNA or mimic/inhibitor for lncRNA-ATB, miR-126, and KRAS.
- Cell viability, migration, invasion, and apoptosis assays were performed.
- Protein levels of apoptosis-related factors and signaling pathways (PI3K/AKT, mTOR) were measured.
- Dual-Luciferase Reporter assay was used to confirm molecular interactions.
Main Results:
- Overexpression of lncRNA-ATB significantly enhanced cell viability, migration, and invasion.
- lncRNA-ATB acts as a molecular sponge for miR-126, leading to its downregulation.
- miR-126 directly targets KRAS, negatively regulating its expression.
- KRAS overexpression promoted cell viability, migration, invasion, and activated PI3K/AKT/mTOR pathways.
Conclusions:
- lncRNA-ATB functions as an oncogene in bladder cancer by promoting proliferation, migration, and invasion.
- The lncRNA-ATB/miR-126/KRAS axis plays a crucial role in bladder cancer progression.
- lncRNA-ATB represents a potential prognostic biomarker and therapeutic target for bladder cancer.
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