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Published on: August 23, 2024
MiR-30d induces apoptosis and is regulated by the Akt/FOXO pathway in renal cell carcinoma
Chenglin Wu1, Bo Jin, Liting Chen
1Department of Biochemistry and Molecular Biology, Health Science Center, Peking University, 38 Xueyuan Road, 100191 Beijing, China.
Abstract:
MicroRNAs (miRNAs) play critical roles in tumorigenesis by modulating the expression of target gene mRNAs. However, their role in cell signaling is not well defined. In this study, we identified miR-30d as a downstream effector of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway in renal cell carcinoma (RCC) cells. We show that Akt inhibition transcriptionally up-regulates miR-30d expression through activation of the transcription factor forkhead box O (FOXO) 3A. Functional analysis revealed that miR-30d overexpression suppresses cell proliferation and induces apoptosis in RCC cells, suggesting that miR-30d acts as a tumor suppressor. In searching for downstream targets of miR-30d, we found that miR-30d post-transcriptionally suppresses expression of the oncoprotein metadherin (MTDH) by destabilizing its mRNA. Furthermore, we found that FOXO down-regulates MTDH expression through up-regulating expression of miR-30d. Thus, our findings reveal a new Akt/FOXO/miR-30d/MTDH signaling transduction pathway and identify miR-30d as a tumor suppressor, providing a new potential target for the treatment of RCC.
Insights
MicroRNAs (miRNAs) are crucial in cancer. This study reveals miR-30d acts as a tumor suppressor in renal cell carcinoma by inhibiting the MTDH oncoprotein via the Akt/FOXO pathway.
Area of Science:
- Molecular Biology
- Oncology
- Cell Signaling
Background:
- MicroRNAs (miRNAs) regulate gene expression and are implicated in tumorigenesis.
- The precise role of miRNAs in cell signaling pathways, particularly in renal cell carcinoma (RCC), remains incompletely understood.
Purpose of the Study:
- To elucidate the role of miR-30d in the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway within RCC.
- To identify downstream targets and regulatory mechanisms of miR-30d in RCC.
Main Methods:
- Investigated miR-30d expression in RCC cells.
- Utilized Akt inhibition and transcription factor analysis (FOXO 3A).
- Performed functional assays for cell proliferation and apoptosis; identified MTDH as a miR-30d target.
Main Results:
- miR-30d is transcriptionally upregulated by Akt inhibition via FOXO 3A activation.
- miR-30d overexpression suppresses RCC cell proliferation and induces apoptosis, indicating tumor suppressor activity.
- miR-30d post-transcriptionally downregulates metadherin (MTDH) by mRNA destabilization.
Conclusions:
- A novel signaling pathway (Akt/FOXO/miR-30d/MTDH) in RCC is identified.
- miR-30d functions as a tumor suppressor in renal cell carcinoma.
- miR-30d represents a potential therapeutic target for RCC treatment.
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