Study identifies potential microRNA target to overcome breast cancer resistance microbiologystudy

A new University of Cincinnati Cancer Center study has identified a particular strand of microRNA as a promising new target for overcoming breast cancer treatment resistance and improving outcomes. The research was recently published in the journal Cancers.

The Cancer Center’s Xiaoting Zhang, Ph.D., said antiestrogen therapy is used for about 75% of breast cancers, but relapse and treatment resistance occur in about half of these patients at some point.

Zhang and his colleagues previously identified a protein called MED1 that is produced in much higher levels in 40% to 60% of breast cancers. MED1 plays key roles in mediating treatment resistance with estrogen receptors (ERs) and the protein HER2, but researchers did not know how it was produced at such a high level to cause treatment resistance.

“With this research, we mainly tried to understand why MED1 is expressing so high in these treatment-resistant breast cancers,” said Zhang, professor and John and Gladys Strauss Endowed Chair in the Department of Cancer Biology in UC’s College of Medicine.

The researchers focused on microRNA, small strands of noncoding genetic material within cells that regulate the expression of different genes. The discovery of microRNA has been awarded the Nobel Prize in Physiology or Medicine in 2024.

“These noncoding RNAs, including microRNAs, are the future,” Zhang said. “Noncoding regions occupy approximately 90% of the human genome—and people used to think they are all junk—but now people realize that these noncoding RNAs transcribed actually play crucial roles, such as regulating proteins’ expression and function.”

The team found that a strand of microRNA called miR-205 has a sequence that can regulate the production of MED1. They further analyzed the human breast cancer database to confirm an inverse correlation between miR-205 and MED1 levels.

“So if MED1 is high, miR-205 is actually low. Essentially, this microRNA will block the production of MED1,” Zhang said. “Then we found they also correlate with treatment outcomes. So if you have low miR-205, now you have high MED1, and the cancer can actually be resistant to the treatment, and you have poor treatment outcomes.”

Researchers also found that miR-205 regulates the protein HER3 in addition to MED1. Part of the four-member HER family of proteins, HER3 is known to work with HER2 to play a role in treatment resistance. Specifically, researchers found that HER3 can regulate the activation of MED1 proteins.

“We not only have more MED1, but more active MED1, so it’s like a double regulation there with this miR-205 regulation of both MED1 and HER3,” Zhang said. “Subsequent studies using in vitro human breast cancer cell lines and in vivo animal models have further confirmed our findings and its functional significance.”

While more research is needed, Zhang said boosting levels of miR-205 could be a different and potentially more effective way to overcome treatment-resistant breast cancers by blocking MED1 production and activity.