Targeting microRNA may benefit some patients with ovarian and breast cancer

A genetic misfire called the 3q26.2 amplicon can cause real havoc. In fact, it is among the most frequent chromosomal aberrations seen in many cancers, including ovarian and breast cancers.

Researchers behind a study at The University of Texas MD Anderson Cancer Center in Houston believe they may have found a molecule-based approach to halting the destructive nature of 3q26.2. By manipulating a noncoding microRNA (miRNA) known as miR569 that is part of the amplicon, scientists were able to increase cell death in vitro and in vivo. MicroRNAs are short, noncoding RNA molecules that are important to controlling gene expression.

The study was published in Cancer Cell (2014; doi:10.1016/j.ccell.2014.10.010).

"Small noncoding miRNAs represent underexplored targets of genetic aberrations and emerging therapeutic targets," said study lead Gordon Mills, MD, PhD, professor and chair of Systems Biology at MD Anderson. "We demonstrated 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."

To halt 3q26.2's penchant for molecular mayhem, miR569 must first alter expression levels of the tumor protein TP53INP1.

"The study results clearly show that TP53INP1 is a key target of miR569 both in vitro and in vivo," said Mills. "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 our 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'," said Mills.

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