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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
MicroRNA-497 suppresses renal cell carcinoma by targeting VEGFR-2 in ACHN cells
Sun Pengcheng1, Wang Ziqi1, Yin Luyao1
1Department of Urology, The Fourth Hospital of Harbin Medical University, Harbin 150001, China.
Abstract:
Abnormal expression of miRNAs contributed to cancers through regulation of proliferation, apoptosis and drug resistance of cancer cells. The present study was designed to investigate the effect of miR-497 on renal cell carcinoma (RCC) and its possible mechanism. Forty paired clear cell RCC (ccRCC) tissues and adjacent normal kidney tissues were obtained from patients, who were not treated by chemotherapy or radiotherapy. RT-PCR was performed to detect expression of miR-497 in the ccRCC tissues. Effects of miR-497 on cell viability, apoptosis, migration and invasion were detected in ACHN cells. Western blotting (WB) was employed to detect the downstream targets of miR-497 We found that miR-497 in ccRCC tissues was decreased. We treated ACHN cells with miR-497 mimics and inhibitors in vitro and found that miR-497 inhibited viability, migration and invasion of ACHN cells. miR-497 promoted ACHN cells' apoptosis. VEGFR-2 was predicted as a possible target of miR-497 Luciferase reporter assay proved that miR-497 suppressed VEGFR-2 directly by binding to its 3'-UTR. Further studies showed that miR-497 influenced the MEK/ERK and p38 MAPK signalling pathways. Our findings demonstrated that miR-497 could suppress RCC by targeting VEGFR-2.
Insights
MicroRNA-497 (miR-497) is downregulated in renal cell carcinoma (RCC). Restoring miR-497 inhibits RCC cell viability, migration, and invasion while promoting apoptosis by targeting VEGFR-2.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) play crucial roles in cancer development, influencing cell proliferation, apoptosis, and drug resistance.
- Aberrant miRNA expression is implicated in various cancers, including renal cell carcinoma (RCC).
Purpose of the Study:
- To investigate the role of miR-497 in renal cell carcinoma (RCC).
- To elucidate the mechanism underlying miR-497's function in RCC, focusing on its potential targets and signaling pathways.
Main Methods:
- Quantitative reverse transcription PCR (RT-PCR) to assess miR-497 expression in ccRCC tissues.
- In vitro studies using ACHN cells treated with miR-497 mimics and inhibitors to evaluate effects on cell viability, apoptosis, migration, and invasion.
- Western blotting (WB) and luciferase reporter assays to identify and validate downstream targets of miR-497.
- Analysis of MEK/ERK and p38 MAPK signaling pathways.
Main Results:
- miR-497 expression was significantly decreased in clear cell RCC (ccRCC) tissues compared to adjacent normal tissues.
- Overexpression of miR-497 in ACHN cells inhibited cell viability, migration, and invasion, while promoting apoptosis.
- VEGFR-2 was identified as a direct target of miR-497, with miR-497 binding to the 3'-UTR of VEGFR-2 and suppressing its expression.
- miR-497 influenced the MEK/ERK and p38 MAPK signaling pathways.
Conclusions:
- miR-497 acts as a tumor suppressor in renal cell carcinoma (RCC).
- The tumor-suppressive effects of miR-497 in RCC are mediated through the direct targeting of VEGFR-2.
- miR-497 may represent a potential therapeutic target for RCC treatment by modulating VEGFR-2 and associated signaling pathways.
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