A rationalized definition of general tumor suppressor microRNAs excludes miR-34a

Abstract

The miR-34a microRNA (miRNA) is currently thought to act as a tumor suppressor: its locus is frequently deleted in human tumors and it is believed to repress cell proliferation. We re-visited the evidence of its anti-cancer activity. Our results show that miR-34a is not generally down-regulated in primary tumors relatively to normal adjacent tissues, and the occasional deletion of miR-34a in human cancers is not due to an anti-tumorigenic activity of that gene, but rather, to its genomic proximity with an actual tumor suppressor. 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. We thus conclude that the generally accepted tumor-suppressive function of miR-34a is erroneous.