Nav: Home

Obesity-associated protein could be linked to leukemia development

December 22, 2016

CINCINNATI--Cancer researchers at the University of Cincinnati (UC) College of Medicine have found an obesity-associated protein's role in leukemia development and drug response which could lead to more effective therapies for the illness.

The study, which will be published in the Dec. 22 online edition of Cancer Cell and led by Jianjun Chen, PhD, associate professor in the Department of Cancer Biology, provided evidence that FTO--the protein associated with fat mass and obesity--plays a critical cancer-promoting role by regulating expression of a set of genes through a mechanism involving ribonucleic acid (RNA) modification and thereby increasing the reproduction of leukemia cells and prohibiting drug response.

"N6-methyladenosine (m6A) RNA methylation, the most prevalent internal modification in messenger RNAs (mRNAs, which translate DNA) in genes, was first identified in 1970s. In 2011, Dr. Chuan He, professor of chemistry at the University of Chicago, a co-senior author of this paper, discovered for the first time that FTO actually functions as an eraser of m6A methylation. This means that it can remove the modification from RNA transcripts, or RNA copies, thereby showing that m6A modification is a reversible process and is highly likely it is of biological importance. In 2012, two groups independently reported the development of novel sequencing technologies to profile all m6A modification areas in the entire genome and showed that roughly one-third of mRNAs in individual mammal cells are targets of m6A modification, highlighting the prevalence and potential functional importance of m6A modification.

"Recent studies have shown that m6A modification in mRNAs or non-coding RNAs plays critical roles in virtually all major normal biological processes such as tissue development and stem cell self-renewal and differentiation. However, little is known about the biological importance of m6A modification in the regulation of cancer-causing genes and/or tumor-suppressing genes in the development of tumors."

Researchers in the study analyzed a microarray dataset of 100 human acute myeloid leukemia (AML) samples from patients and nine normal control samples as well as other large-scale microarray datasets of AML samples. They found that FTO was highly expressed in various subtypes of leukemia samples such as those that contained chromosome crossover (genetic exchange between chromosomes) or mutations in certain genes. The high level of FTO expression contributed to cancer cells multiplying and surviving and also promoted the development of leukemia in animal models and the non-response of cancer cells to therapeutic agents.

Additionally, researchers found that genes like ASB2 and RARA, which were reported to inhibit leukemia cell growth and/or mediate the response of leukemia cells to therapeutic agents, were suppressed in the AML samples with higher FTO expression. The suppression of these genes was attributed to FTO-controlled decreased stability of their mRNA and was connected to FTO's m6A demethylase activity.

"Our study shows, for the first time, the functional importance of the m6A modification machinery in leukemia," says Chen. "In addition, given the functional importance of FTO in the formation of leukemia and drug response, targeting FTO signaling may present a new therapeutic strategy to treat leukemia. As FTO may also play a cancer-promoting role in various types of solid tumors, besides leukemia, our discoveries may have a broad impact in cancer biology and cancer therapy. Further studies are needed to advance our understanding of the critical role of FTO in various types of cancers and to develop more effective novel therapeutic strategies based on such understanding to treat cancers."
-end-
In addition to researchers from the University of Cincinnati, scientists from Howard Hughes Medical Institute and the University of Chicago; Baylor College of Medicine; and the First Affiliated Hospital Zhejiang University, Wuhan University and Sun Yat-Sen University Cancer Center, all in China, were involved in the study.

This study was funded by the National Institutes of Health (CA178454, CA182528,CA214965 and GM071440), the Leukemia & Lymphoma Society, the American Cancer Society, Howard Hughes Medical Institute, the Damon Runyon Cancer Research Foundation, the China Scholarship Council and the Foundation of Innovation Team for Basic and Clinical Research of Zhejiang Province. The authors cite no conflict of interest.

University of Cincinnati Academic Health Center

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)

The Emperor of All Maladies: A Biography of Cancer
by Siddhartha Mukherjee (Author)

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

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

How to Starve Cancer
by Jane McLelland (Author)

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

Chris Beat Cancer: A Comprehensive Plan for Healing Naturally
by Hay House Inc.

Radical Remission: Surviving Cancer Against All Odds
by Kelly A. Turner PhD (Author)

Keto for Cancer: Ketogenic Metabolic Therapy as a Targeted Nutritional Strategy
by Miriam Kalamian EdM MS CNS (Author), Thomas N. Seyfried (Foreword)

90 Days to Live: Beating Cancer When Modern Medicine Offers No Hope (Part of the Attacking Cancer)
by Rodney Stamps (Author), Paige Stamps (Author)

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Don't Fear Math
Why do many of us hate, even fear math? Why are we convinced we're bad at it? This hour, TED speakers explore the myths we tell ourselves and how changing our approach can unlock the beauty of math. Guests include budgeting specialist Phylecia Jones, mathematician and educator Dan Finkel, math teacher Eddie Woo, educator Masha Gershman, and radio personality and eternal math nerd Adam Spencer.
Now Playing: Science for the People

#517 Life in Plastic, Not Fantastic
Our modern lives run on plastic. It's in the computers and phones we use. It's in our clothing, it wraps our food. It surrounds us every day, and when we throw it out, it's devastating for the environment. This week we air a live show we recorded at the 2019 Advancement of Science meeting in Washington, D.C., where Bethany Brookshire sat down with three plastics researchers - Christina Simkanin, Chelsea Rochman, and Jennifer Provencher - and a live audience to discuss plastics in our oceans. Where they are, where they are going, and what they carry with them. Related links:...