Potential microRNA therapies targeting Ras, NFkappaB and p53 signaling.
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by binding to complementary sequences in mRNAs encoding downstream target genes. A large variety of cellular processes, including differentiation, development, apoptosis and cell cycle progression, are dependent on miRNA-mediated suppression of gene expression for their regulation. As such, it is unsurprising that these small RNA molecules are associated with signaling networks that are often altered in various diseases, including cancer. This review focuses on the function of miRNAs in three of the most well-documented signaling pathways that are dysregulated in tumors: the NFkappaB and Ras prosurvival signaling cascades and the tumor suppressor p53 pathway. Recent findings that connect these pathways through various miRNA families are reviewed, and support for using miRNA therapy as a novel method to counteract these tumor-promoting signaling events are presented.
Kasinski
Andrea L
AL
Yale University, Department of Molecular, Cellular and Developmental Biology, 66 Whitney Avenue, KBT 936, PO Box 208103, New Haven, CT 06520, USA.
Slack
Frank J
FJ
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D016328:NF-kappa B / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism*
C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; C474488:let-7 microRNA, C elegans; D018631:ras Proteins