RNA tags may hold a key to cancer

Chuan He
Chuan He, Phd

Even just a decade ago, scientists didn’t know that RNA molecules — encoded by DNA and made into proteins that carry out cell processes — were sometimes tagged with modifications like molecular barcodes and that these tags could impact RNA expression and function. These discoveries have transformed our view of the RNA code and opened up a new field in cancer research.

In 2011, the laboratory of University of Chicago Medicine Comprehensive Cancer Center investigator Chuan He, PhD, identified the first known enzyme responsible for removing an RNA tag called N6-methyladenosine (m6A). Since then, He has identified other tag “erasers” (removes tags), discovered some tag “writers” (adds tags), and collaborated with other Comprehensive Cancer Center faculty to interrogate the importance of these players in cancer.

A study involving He’s laboratory and gynecologic oncologist Ernst Lengyel, MD, PhD, reported that 70% of endometrial cancers have reduced levels of m6A methylation because of mutations or reduced expression of components of the “writer” complex.

Because of these alterations, the cancer cells are able to grow faster and form tumors more easily. By dissecting the precise molecular networks disrupted as a result, the team hopes to be able to use drugs to block or slow down tumor growth.

Additionally, in collaboration with gasteroenterologist and researcher B. Marc Bissonnette, MD, He has shown that these tagged RNA molecules contribute to the development of colorectal cancer. The team received a large grant from the National Cancer Institute (NCI) to understand the molecular players involved and further their development of a novel sensitive biomarker for colorectal cancer based on RNA tags uniquely found in tumor cells but not surrounding normal tissue.

To further these research efforts and train future experts in this field, He and Tao Pan, PhD, established the Center for Dynamic RNA Epitranscriptomes through a grant from the National Institutes of Health (NIH). This center focuses on developing technologies to decode RNA tags and is one of only eight Centers of Excellence in Genomic Science established, and the only one dedicated to RNA modifications.

Generous support by the University of Chicago Cancer Research Foundation Women’s Board in 2017 and 2018 has also fostered research in cancer RNA epitranscriptomics. Pilot project grants awarded included one to Yu-Ying He, PhD, for her collaborative project with Chuan He focused on mapping and targeting m6A modifications in skin cancer.

Already, this funding has been instrumental for securing larger grants from the NIH to extend the science, pushing the boundaries of knowledge, and ensuring the Comprehensive Cancer Center will remain a leader in the field for years to come.