Abstract
While several microRNAs (miRNAs) have been proposed to act as tumor suppressors, a consensual definition of tumor suppressing miRNAs is still missing. Similarly to coding genes, we propose that tumor suppressor miRNAs must show evidence of genetic or epigenetic inactivation in cancers, and exhibit an anti-proliferative activity under endogenous expression levels. Here we observe that this definition excludes the most extensively studied tumor suppressor candidate miRNA, miR-34a. In analyzable cancer types, miR-34a does not appear to be down-regulated in primary tumors relatively to normal adjacent tissues. Deletion of miR-34a is occasionally found in human cancers, but it does not seem to be driven by an anti-tumorigenic activity of the miRNA, since it is not observed upon smaller, miR-34a-specific alterations. Its anti-proliferative action was observed upon large, supra-physiological transfection of synthetic miR-34a in cultured cells, and our data indicates that endogenous miR-34a levels do not have such an effect. Our results therefore argue against a tumor suppressive function for miR-34a, providing an explanation to the lack of efficiency of synthetic miR-34a administration against solid tumors.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
New implementation of the miRNA expression analysis in primary tumors (Figure 1A), which does not change the results but changes the arbitrary order of columns in the heatmap. Addition of a supplementary figure (now Suppl. Figure 6) showing the determination of the IC50 of doxorubicin in HCT-116 cells. Edition of the text (in the abstract and in the discussion) to mention the possibility that miR-34a may act as a tumor suppressor in some yet-to-be-analyzed cancer types.
