Nav: Home

Circular RNA limits skin cancer spread

January 13, 2020

A mysterious piece of genetic material restrains the spread of skin cancer cells, but is frequently lost as they mature, a new study finds.

Published online January 13 in Cancer Cell, the new work revolves around circular RNA, a recently described type of ribonucleic acid (RNA). Typically, DNA blueprints are converted into RNA and then into proteins with cellular functions. While most RNA are linear molecules, some form circles when their ends loop around and attach.

Instead of encoding proteins, circular RNA (circRNA) seem to be part of complex regulatory systems, but their functions are still unclear, say the study authors.

Led by researchers at NYU Grossman School of Medicine, the study in cell cultures and mice is the first to show that a circRNA called CDR1as blocks the aggressive spread of melanoma cancers, and that its loss promotes it. A study analysis of human melanoma tissues also linked higher CDR1as levels with increased survival.

In patients that die from melanoma, the most lethal form of skin cancer, the aggressive spread, or metastasis, of cancer cells is the primary cause of death. Cancer cells arise from normal cells because of genetic errors, but changes in DNA do not fully explain how the cells spread.

"Our study provides new insights into the aggressive behavior of melanoma, and is the first to expose a circRNA as a suppressor of metastasis," says senior study author Eva Hernando, PhD, associate professor in the Department of Pathology at NYU Langone Health.

"We found CDR1as restrains a known pro-cancer protein called IGF2BP3, revealing a new function of CDR1as that may have therapeutic implications," adds first author Douglas Hanniford, PhD, an instructor in the same department.

Spread Follows Loss of Restraint

Recent work had suggested previously unknown functions for circRNAs, including their binding with proteins that attach to RNA to influence cell functions. Specifically, the new study reveals that metastasis of melanomas proceeds when the interaction between CDR1as and the RNA-binding protein IGF2BP3 is disrupted.

If CDR1as is active, researchers say, IGF2BP3 proteins bind to its circular RNA molecules, instead of attaching to other RNAs that code for pro-metastatic proteins. When CDR1as was removed using molecular techniques, IGF2BP3 was free to promote cancer cell invasion, which occurs when cells penetrate skin layers and spread to distant organs.

The study identifies the source of CDR1as in cells as LINC00632, an example of yet another class of RNA called long non-coding RNA. Experiments revealed further that an "epigenetic" mechanism in melanoma cells silences the LINC00632 gene, which halts CDR1as production.

Epigenetic changes adjust the operation of genes without changing their DNA code, researchers say. These include the attachment of molecules called methyl groups to histones, the "spools" around which DNA chains are wrapped. Methylation status determines whether a given stretch of DNA is unwound and accessible; or instead compacted, with the genes residing there silenced, researchers say.

The new study found that a particular histone methylation, H3K27me3, silences the gene for LINC00632 in melanoma cells starting to spread, which come to lack CDR1as. The authors say that this interaction could represent a mechanism that helps cells migrate during normal (fetal) development, but that then drives cancer spread when it mistakenly re-occurs in tumors.
-end-
The study will go alive at this link when it is published on Monday at 11 am US EDT:

https://www.cell.com/cancer-cell/fulltext/S1535-6108(19)30577-X

Along with Hernando, study authors in the Department of Pathology at NYU Langone were first author Douglas Hanniford, Alejandro Ulloa, Alcida Karz, Rana Moubarak, Maria Gabriela Berzoti-Coelho, Veronica Davalos, Karin Lilja, Jochen Imig, Andreas Kloetgen, and Iannis Aifantis. Also, NYU authors were Iman Osman in Departments of Urology and Medicine, Pamela Wu in the Institute for Systems Genetics, and Varshini Vasudevaraja of the Applied Bioinformatics Lab. Also authors were Beatriz Sánchez-Sendra and Carlos Monteagudo of the University of Valencia, Spain; Tommaso Tabaglio and Ernesto Guccione of the Icahn School of Medicine at Mount Sinai, previously at A*STAR in Singapore.

The study was supported by National Institutes of Health grants R01CA155234, R01CA163891, R01CA2022027, T32 CA009161-37, P30CA016087, S10OD01058 and S10OD018338; as well as by U.S. Department of Defense grant W81XWH-16-1-0437, Sào Paulo Research Foundation grant 2017/23501-6, Instituto de Salud Carlos III grants PI13/02786 and PI17/02019, FEDER European funds, and the Regional Valencian Ministry of Education PROMETEO grant II/2015/009.

NYU Langone Health / NYU School of Medicine

Related Science Articles:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.
Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.
Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.
Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.
Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.
World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.
PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.
Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.
Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.
Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.
More Science News and Science Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Teaching For Better Humans 2.0
More than test scores or good grades–what do kids need for the future? This hour, TED speakers explore how to help children grow into better humans, both during and after this time of crisis. Guests include educators Richard Culatta and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
Now Playing: Science for the People

#556 The Power of Friendship
It's 2020 and times are tough. Maybe some of us are learning about social distancing the hard way. Maybe we just are all a little anxious. No matter what, we could probably use a friend. But what is a friend, exactly? And why do we need them so much? This week host Bethany Brookshire speaks with Lydia Denworth, author of the new book "Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond". This episode is hosted by Bethany Brookshire, science writer from Science News.
Now Playing: Radiolab

Space
One of the most consistent questions we get at the show is from parents who want to know which episodes are kid-friendly and which aren't. So today, we're releasing a separate feed, Radiolab for Kids. To kick it off, we're rerunning an all-time favorite episode: Space. In the 60's, space exploration was an American obsession. This hour, we chart the path from romance to increasing cynicism. We begin with Ann Druyan, widow of Carl Sagan, with a story about the Voyager expedition, true love, and a golden record that travels through space. And astrophysicist Neil de Grasse Tyson explains the Coepernican Principle, and just how insignificant we are. Support Radiolab today at Radiolab.org/donate.