Send to

Choose Destination
See comment in PubMed Commons below
Cell Signal. 2013 May;25(5):1212-21. doi: 10.1016/j.cellsig.2013.01.028. Epub 2013 Feb 15.

MiR-30d induces apoptosis and is regulated by the Akt/FOXO pathway in renal cell carcinoma.

Author information

Department of Biochemistry and Molecular Biology, Health Science Center, Peking University, 38 Xueyuan Road, 100191 Beijing, China.


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.

[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center