In a study, scientists found a molecule-based approach to halting a genetic fault called 3q26.2 amplicon, which can cause real havoc. By manipulating a non-coding microRNA (miRNA) known as miR569 that is part of the amplicon, scientists were able to increase cell death in vitro and in vivo. For many cancers, including ovarian and breast cancers, the amplicon carries the most frequent chromosomal aberrations.

As known in the biomedical circle, MicroRNAs are short, non-coding RNA molecules that are important to controlling gene expression. The molecules can represent underexplored targets of genetic aberrations and emerging therapeutic targets.

The study showed that miR569, which is overexpressed in a subset of ovarian and breast cancers due in part to the 3q26.2 amplicon, can impact cell survival and proliferation. In order for miR69 to halt 3q26.2′s penchant for molecular mayhem, it must first alter expression levels of the tumor protein known as TP53INP1.

It is clearly demonstrated that TP53INP1 is a key target of miR569 both in vitro and in vivo. An increase in miR569 levels subsequently decreased TP53INP1 levels which was associated with worsened outcomes for ovarian patients.

However, when miR569 expression was “silenced” or decreased, TP53INP1 levels were increased and survivability outcomes improved. In effect, targeting miR569 sensitizes ovarian and breast cancer cells overexpressing miR569 to the commonly used chemotherapy agent cisplatin, which impacts its effectiveness.

The discovery that miRNAs are potent regulators of RNA stability and translation dramatically change current understanding of the mechanisms controlling protein levels, and further provided a therapeutic approach to a number of targets that have previously been designated as ‘undruggable’.