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miR-34: from bench to bedside
Massimiliano Agostini1, Richard A Knight
1Medical Research Council, Toxicology Unit, Leicester University, Leicester, UK.
Abstract:
The mir-34 family was originally cloned and characterized in 2007 as a p53 target gene. Almost immediately it became clear that its major role is as a master regulator of tumor suppression. Indeed, when overexpressed, it directly and indirectly represses several oncogenes, resulting in an increase of cancer cell death (including cancer stem cells), and in an inhibition of metastasis. Moreover, its expression is deregulated in several human cancers. In 2013, a miR-34 mimic has become the first microRNA to reach phase 1 clinical trials. Here we review the miR-34 family and their role in tumor biology, and discuss the potential therapeutic applications of miR-34a mimic.
Insights
The miR-34 family acts as a master tumor suppressor by targeting oncogenes, inhibiting cancer growth, and metastasis. miR-34a mimics are being explored for cancer therapy.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- The miR-34 family, identified as p53 target genes in 2007, are key regulators of tumor suppression.
- Dysregulation of miR-34 expression is observed in numerous human cancers, highlighting its clinical relevance.
Purpose of the Study:
- To review the miR-34 family's role in tumor biology.
- To discuss the therapeutic potential of miR-34a mimics in cancer treatment.
Main Methods:
- Literature review of studies on miR-34 family function and cancer.
- Analysis of miR-34a mimic clinical trial data.
Main Results:
- Overexpression of miR-34 family members represses oncogenes, leading to cancer cell death and reduced metastasis.
- miR-34a mimics have shown promise, with one reaching Phase 1 clinical trials in 2013.
Conclusions:
- The miR-34 family is a critical tumor suppressor pathway with significant implications in cancer.
- miR-34a mimics represent a promising therapeutic strategy for various human cancers.
