Gordon Mills, MD, PhD, a professor at The University of Texas MD Anderson Cancer Center, is finding ways to control the growth of breast and ovarian cancer tumors. His team recently published an investigation on a molecule-based approach that inhibits the destructive behavior of the genetic alteration known as the 3q26.2 amplicon using the non-coding microRNA miR569.
“Small non-coding miRNAs represent underexplored targets of genetic aberrations and emerging therapeutic targets,” Dr. Mills said in an MD Anderson news release. “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.”
The research behind this finding was published in Cancer Cell, under the title “Copy Number Gain of hsa-miR-569 at 3q26.2 Leads to Loss of TP53INP1 and Aggressiveness of Epithelial Cancers.” During the study, the researchers, including lead study author Pradeep Chaluvally-Raghavan, PhD, identified a mechanism of cancer cell proliferation that involved miR569 and tumor protein TP53INP1.
“The study results clearly show that TP53INP1 is a key target of miR569 both in vitro and in vivo,” Dr. Mills added. “An increase in miR569 levels subsequently decreased TP53INP1 levels which was associated with worsened outcomes for ovarian patients.”
To combat this change, the team silenced miR569, and they saw an increase in T53INP1 protein levels. The animal model of cancer also experienced enhanced survivability. Adding to this benefit, silencing miR569 sensitized breast cancer and ovarian cells to cisplatin, a chemotherapy agent.
“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 Dr. Mills.
Previous and ongoing research efforts in other laboratories have investigated delivering silencing RNA to cells in vitro and in vivo, making Dr. Mills’ findings applicable to create a new treatment for breast cancer that focuses on silencing miR569.