Nav: Home

DNA looping architecture may lead to opportunities to treat brain tumors

September 11, 2017

The discovery of a mechanism by which normal brain cells regulate the expression of the NFIA gene, which is important for both normal brain development and brain tumor growth, might one day help improve therapies to treat brain tumors. The study appears in the journal Nature Neuroscience.

"We began this project by studying how three components that regulate the expression of the NFIA gene interact with each other in the developing spinal cord in animal models," said corresponding author Dr. Benjamin Deneen, associate professor of neuroscience at the Center for Stem Cell and Regenerative Medicine and member of the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine.

The researchers studied mostly glial cells, which represent 70 percent of the cells in the central nervous system and support the functions of the neurons.

Gene expression, the process by which genes produce proteins, is regulated at different levels, in a coordinated fashion, but scientists don't completely understand how these levels interact. Deneen and his colleagues explored how three levels of gene regulation coordinated their activities to regulate NFIA gene expression. The researchers studied enhancers, (sections of DNA that are located at a distance from the NFIA gene and can influence gene expression), transcription factors (proteins that bind to enhancers) and the three-dimensional architecture of the associated DNA.

First, they identified enhancers involved in the regulation of expression of NFIA gene using a non-traditional approach. Instead of using bioinformatics to infer which sections of DNA probably have enhancer activity, they used living chick embryos to identify enhancer elements in the spinal cord associated with the expression of the NFIA gene.

"Our chick spinal cord system is a powerful model for screening and proving enhancer function," said Deneen, who also is a member of Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital. "The system allowed us to identify multiple enhancers that operate in specific locations in the DNA and at different times, enabling us to pinpoint the transcription factors that regulate them. We also were able to determine how the DNA strands formed distinct 3-D architectures - DNA loops - that brought enhancers and transcription factor together closer to the NFIA gene, which led to the production of the NFIA protein."

Applying the new findings to glioma, a type of brain tumor derived from glial cells

"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."
-end-
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 Hospital, 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.

Baylor College of Medicine

Related Cancer Articles:

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Cancer expert says public health and prevention measures are key to defeating cancer
Is investment in research to develop new treatments the best approach to controlling cancer?
UI Cancer Center, Governors State to address cancer disparities in south suburbs
The University of Illinois Cancer Center and Governors State University have received a joint four-year, $1.5 million grant from the National Cancer Institute to help both institutions conduct community-based research to reduce cancer-related health disparities in Chicago's south suburbs.
Leading cancer research organizations to host international cancer immunotherapy conference
The Cancer Research Institute, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology, and the American Association for Cancer Research will join forces to sponsor the first International Cancer Immunotherapy Conference at the Sheraton New York Times Square Hotel in New York, Sept.

Related Cancer Reading:

The Cancer-Fighting Kitchen, Second Edition: Nourishing, Big-Flavor Recipes for Cancer Treatment and Recovery
by Rebecca Katz (Author), Mat Edelson (Author)

This new and revised edition of the IACP award-winning cookbook brings the healing power of delicious, nutritious foods to those whose hearts and bodies crave a revitalizing meal, through 150 new and updated recipes.

Featuring science-based, nutrient-rich recipes that are easy to prepare and designed to give patients a much-needed boost by stimulating appetite and addressing treatment side effects including fatigue, nausea, dehydration, mouth and throat soreness, tastebud changes, and weight loss. A step-by-step guide helps patients nutritionally prepare for all phases of... View Details


Anticancer: A New Way of Life
by David Servan-Schreiber MD PhD (Author)

The revolutionary, New York Times bestselling guide to the powerful lifestyle changes that fight and prevent cancer—an integrative approach based on the latest scientific research
 
“A common-sense blueprint for healthy living.” —Chicago Tribune
 
“Resonating with cancer support communities and recommended nationwide.” —Los Angeles Times
 
“Life affirming . . . filled with practical advice.” —The Seattle Times
 
David Servan-Schreiber was a rising... View Details


The Truth about Cancer: What You Need to Know about Cancer's History, Treatment, and Prevention
by Ty M Bollinger (Author)

Cancer touches more lives than you may think. According to the World Health Organization, one out of three women alive today, and one out of two men, will face a cancer diagnosis in their lifetime.

To Ty Bollinger, this isn’t just a statistic. It’s personal. After losing seven members of his family to cancer over the course of a decade, Ty set out on a global quest to learn as much as he possibly could about cancer treatments and the medical industry that surrounds the disease. He has written this book to share what he’s uncovered—some of which may shock you—and to give you... View Details


Tripping over the Truth: How the Metabolic Theory of Cancer Is Overturning One of Medicine's Most Entrenched Paradigms
by Travis Christofferson (Author), Dominic D'Agostino (Foreword)

With a new foreword by Dr. Dominic D'Agostino, PhD and epilogue by the author

 A masterful synchronization of history and cutting-edge science shines new light on humanity's darkest diagnosis.

In the wake of the Cancer Genome Atlas project's failure to provide a legible roadmap to a cure for cancer, science writer Travis Christofferson illuminates a promising blend of old and new perspectives on the disease. Tripping over the Truth follows the story of cancer’s proposed metabolic origin from the vaunted halls of the German scientific golden age to... View Details


Cancer: 50 Essential Things to Do: 2013 Edition
by Greg Anderson (Author)

The ground-breaking classic guide to surviving cancer?now completely updated!

Revised and updated for the first time since 1999, this invaluable guide to cancer recovery offers an easily accessible plan for patients and family members. Written by a cancer survivor, the book is an inspiring, action-oriented roadmap for those who choose to adopt a stance of hope and take charge of their diagnosis.

With penetrating insights that bring together more than two decades of scientifically supported research and experience, Anderson reveals a step-by-step holistic action plan... View Details


Living with Cancer: A Step-by-Step Guide for Coping Medically and Emotionally with a Serious Diagnosis (A Johns Hopkins Press Health Book)
by Vicki A. Jackson (Author), David P. Ryan (Author), Michelle D. Seaton (Author)

The prospect of entering treatment is overwhelming for anyone facing a diagnosis of cancer. While patients have access to a vast amount of medical information online, this advice is often unreliable or confusing. In Living with Cancer, Drs. Vicki A. Jackson and David P. Ryan have crafted the first step-by-step guide aimed at helping people with this life-defining disease grasp what’s happening to them while coping physically and emotionally with cancer treatment.

An empathetic resource full of relatable patient stories, this book teaches patients and caregivers how to ask... View Details


Cancer Hates Tea: A Unique Preventive and Transformative Lifestyle Change to Help Crush Cancer
by Maria Uspenski (Author), Dr. Mary L. Hardy (Foreword)

Drink Tea to Tell Cancer ‘Hit the Road’

Become a tea lover with a purpose and help your body defend itself against cancer. Learn to embrace tea in all its varieties― green, white, black, pu-erh, herbal and more―as both a mental and physical experience to protect your health. Discover the history, growing information and health implications of each variety, as well as uniquely delicious methods to boost your intake with serving suggestions, food pairings and recipes that highlight the benefits of tea.

After her own battle with cancer, Maria Uspenski extensively... View Details


F*ck Cancer: A totally inappropriate self-affirming adult coloring book (Totally Inappropriate Series) (Volume 4)
by Jen Meyers (Author)

*A portion of the proceeds from this book will be donated to support research dedicated to finding a cure for cancer. Because fuck cancer.

This book is for you.

If you are fighting cancer, this is for you. If your brother, sister, mom, dad, son, daughter, relative, or friend is fighting cancer, this is for you. If you've lost someone to cancer like I have, this is for you. If cancer affects your life in any way, this is for you.

The stress of cancer can feel crushing. But perhaps this book can help you get away from it all, if only for a little... View Details


Anti-Cancer Smoothies: Healing With Superfoods: 35 Delicious Smoothie Recipes to Fight Cancer, Live Healthy and Boost Your Energy
by Linda H. Harris (Author)

Anti-Cancer Diet, Cancer Fighting Foods, and Cancer Nutrition

Whether you have cancer or you're at risk of cancer because of your family history - the way you eat can have a major impact on your health and your ability to fight or manage your disease. Cancer is notorious for sapping the strength and nutrition out of a person's body. You'll need to replace a lot of the vitamins, nutrients and minerals that certain drugs and treatments deplete.

The Anti-Cancer Smoothies in this book are made of healthy and tasty vegetables, fruits, spices and herbs that are known to fight cancer.... View Details


Beating Cancer with Nutrition (Fourth Edition) Rev
by Patrick Quillin (Author)

There is good news in the "war on cancer". Optimal nutrition coupled with appropriate medical treatment can dramatically improve the quality and quantity of life and chances for a complete remission for most cancer patients. A well-nourished cancer patient can better manage the disease. Cancer is the number two cause of death in America and the developed nations of the world with one out of four dying from cancer and 38% of women and 43% of men projected to develop cancer over their lifetime. While the overall death rate from cancer has not appreciably declined since... View Details

Best Science Podcasts 2017

We have hand picked the best science podcasts for 2017. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Simple Solutions
Sometimes, the best solutions to complex problems are simple. But simple doesn't always mean easy. This hour, TED speakers describe the innovation and hard work that goes into achieving simplicity. Guests include designer Mileha Soneji, chef Sam Kass, sleep researcher Wendy Troxel, public health advocate Myriam Sidibe, and engineer Amos Winter.
Now Playing: Science for the People

#448 Pavlov (Rebroadcast)
This week, we're learning about the life and work of a groundbreaking physiologist whose work on learning and instinct is familiar worldwide, and almost universally misunderstood. We'll spend the hour with Daniel Todes, Ph.D, Professor of History of Medicine at The Johns Hopkins University, discussing his book "Ivan Pavlov: A Russian Life in Science."