UF team discovers new role of protein in head and neck cancer cell growth

A University of Florida research team has discovered a new role of a key protein in driving changes in the genetic material of cells, which can contribute to the development of cancer. The findings could pave the way for new therapeutic targets for head and neck cancers.

“We found that two proteins play an important role in tumor growth in head and neck cancer by forming a complex with each other and regulating changes in RNA,” said Zhijian Qian, Ph.D., the Pierre Chagnon Professor of Cancer Research in the division of hematology and oncology in the UF College of Medicine. “We further demonstrated that suppressing either protein could significantly inhibit head and neck cancer cell growth in vitro and in mice, indicating that the proteins could be therapeutic targets for these cancers.”

Qian, a member of the UF Health Cancer Center’s Mechanisms of Oncogenesis research program, is the lead author of the study, published May 30 in the journal Molecular Cell.

Head and neck cancers usually begin in the cells that line the surfaces of the head and neck, such as those inside the mouth, throat and voice box.

Inside cells, mRNA can undergo modifications in a process called mRNA demethylation. RNA binding proteins play a vital role in these processes, which influence genetic expression. Disruptions in the regulation of these processes has been associated with a variety of diseases in humans, including cancer.

In the new study, the team set out to determine how one unstudied RNA binding protein, RBM33, works in mRNA methylation. Little was known about how RMB33 worked in cancer. The researchers found that RBM33 plays a critical role in the mRNA demethylation process by forming a complex with another protein. The team further uncovered the mechanism by which RBM33 regulates a key gene involved in head and neck cancer cell growth.

“If we can target the interaction between these two proteins, we can efficiently and selectively inhibit tumor cell growth,” Qian said.

To reach their conclusions, the team used various cell types, as well as samples of primary head and neck cancer tumors from patients. The study builds on the group’s prior work assessing mRNA methylation in leukemia. Further studies are needed to determine whether the new complex could have a role in other types of cancer, Qian said.

The study’s first author is Fang Yu, Ph.D., a postdoctoral researcher at UF who was recently promoted to a research assistant professor in Qian’s lab. Co-first authors include collaborators from the laboratory of Chuan He, Ph.D., a well-known scientist in the field of RNA biology from the University of Chicago.