“We extended these studies to glioma, one of the most deadly forms of cancer. It has a 5 year progression-free survival rate of less than 5 percent,” Deneen said.
“We had previously shown that NFIA is important for glioma formation,” said first author Dr. Stacey Glasgow, a postdoctoral fellow in the Deneen lab. “In this study we wanted to know whether the 3-D DNA loops we saw in normal glial cells also formed in glioma and what would happen if we disrupted them.”
The researchers found that the DNA loops they had observed in normal glial cells also were present in glioma cells. When they disrupted the DNA loops in normal glial cells, the cells did not express the NFIA gene and did not fulfill their expected development. When the researchers disrupted the DNA loops in glioma cells, the cells decreased the expression of NFIA and reduced proliferation.
“Altogether, our results open the possibility for a new approach to treat glioma in the future,” Deneen said. “Disrupting the DNA loops required for NFIA expression could be a potential strategy to indirectly reduce NFIA expression and, as a result, reduce tumor proliferation.”
Other contributors to this work were Jeffrey C Carlson, Wenyi Zhu, Lesley S Chaboub, Peng Kang, Hyun Kyoung Lee, Yoanne M Clovis, Brittney Lozzi, Robert J McEvilly, Michael G Rosenfeld, Chad J Creighton, Soo-Kyung Lee and Carrie Mohila. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, Texas Children’s Hospita, Dan L Duncan Comprehensive Cancer Center, Papé Family Pediatric Research Institute Portland, Oregon Health & Science University and the University of California San Diego.
This work was supported by grants from the National Institutes of Health (NS071153, K01CA190235 and 5-T32HL092332-08), Cancer Prevention Research Institute of Texas (RP150334 and RP160192), and Sontag Foundation.