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Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
Exosomal microRNA-15a from ACHN cells aggravates clear cell renal cell carcinoma via the BTG2/PI3K/AKT axis
Dao-Yuan Li1, Fei-Fei Lin2, Guo-Ping Li1
1Department of Urology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, China.
Abstract:
Accumulating studies have indicated that exosomal microRNAs (miRNAs/miRs) can mediate clear cell renal cell carcinoma (ccRCC) at the early stage, but the mechanisms remain to be specified. Here, we investigated the mechanism of exosomal miR-15a in ccRCC. After successful isolation of exosomes from RCC cells, we found that miR-15a was upregulated in ccRCC cells. Moreover, upregulation of miR-15a by pre-miR-15a promoted the proliferation, migration, invasion, and epithelial-mesenchymal transition of ccRCC cells. A luciferase assay revealed that B-cell translocation gene 2 (BTG2) was a target gene of miR-15a and negatively correlated with miR-15a expression. BTG2 was poorly expressed in ccRCC, which reduced the proliferation of ccRCC cells. In addition, overexpression of BTG2 could reverse the promotive effects of miR-15a on ccRCC. Furthermore, BTG2 reduced PI3K/AKT pathway activity. Our results collectively indicated that exosomal miR-15a from RCC cells accelerated cell viability by downregulating BTG2 and promoting the activity of the PI3K/AKT signaling pathway. We demonstrated a novel mechanism by which exosomal miR-15a exerted pro-proliferatory effects on ccRCC, highlighting the potential of exosomal miR-15a as a target for ccRCC prognosis.
Insights
Exosomal microRNAs (miRNAs) drive clear cell renal cell carcinoma (ccRCC) progression. This study reveals exosomal miR-15a promotes ccRCC by downregulating BTG2 and activating the PI3K/AKT pathway, offering a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Exosomal microRNAs (miRNAs) play a role in clear cell renal cell carcinoma (ccRCC) pathogenesis.
- The specific mechanisms by which miRNAs contribute to early-stage ccRCC remain largely undefined.
Purpose of the Study:
- To investigate the mechanism of exosomal miR-15a in ccRCC.
- To identify the downstream targets and signaling pathways regulated by exosomal miR-15a in ccRCC.
Main Methods:
- Exosome isolation from renal cell carcinoma (RCC) cells.
- Quantitative real-time PCR to measure miR-15a expression.
- Luciferase reporter assay to confirm BTG2 as a miR-15a target.
- Cell proliferation, migration, and invasion assays.
- Western blotting to assess PI3K/AKT pathway activity.
Main Results:
- miR-15a was found to be upregulated in ccRCC cells and exosomes.
- Overexpression of miR-15a promoted ccRCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition.
- B-cell translocation gene 2 (BTG2) was identified as a direct target of miR-15a and was downregulated in ccRCC.
- BTG2 overexpression reversed the pro-tumorigenic effects of miR-15a and inhibited the PI3K/AKT pathway.
Conclusions:
- Exosomal miR-15a accelerates ccRCC progression by downregulating BTG2 and activating the PI3K/AKT signaling pathway.
- Exosomal miR-15a represents a potential diagnostic and therapeutic target for ccRCC.
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