Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

MicroRNA helps cancer evade immune system

19.09.2017

The immune system automatically destroys dysfunctional cells such as cancer cells, but cancerous tumors often survive nonetheless. A new study by Salk scientists shows one method by which fast-growing tumors evade anti-tumor immunity.

The Salk team uncovered two gene-regulating molecules that alter cell signaling within tumor cells to survive and subvert the body's normal immune response, according to a September 18, 2017, paper in Nature Cell Biology. The discovery could one day point to a new target for cancer treatment in various types of cancer.


Salk researchers discover how oxygen-deprived tumors survive body's immune response. Here, visible regions of hypoxia in tumor samples correlate with cell signaling linked to suppressing the immune system.

Credit: Salk Institute


Salk researchers discover how oxygen-deprived tumors survive body's immune response. Juan Carlos Izpisua Belmonte is pictured.

Credit: Salk Institute

"The immunological pressure occurring during tumor progression might be harmful for the tumor to prosper," says Salk Professor Juan Carlos Izpisua Belmonte, senior author of the work and holder of the Roger Guillemin Chair. "However, the cancer cells find a way to evade such a condition by restraining the anti-tumor immune response."

Cancerous tumors often grow so fast that they use up their available blood supply, creating a low-oxygen environment called hypoxia. Cells normally start to self-destruct under hypoxia, but in some tumors, the microenvironment surrounding hypoxic tumor tissue has been found to help shield the tumor.

"Our findings actually indicate how cancer cells respond to a changing microenvironment and suppress anti-tumor immunity through intrinsic signaling," says Izpisua Belmonte. The answer was through microRNAs.

MicroRNAs--small, noncoding RNA molecules that regulate genes by silencing RNA--have increasingly been implicated in tumor survival and progression. To better understand the connection between microRNAs and tumor survival, the researchers screened different tumor types for altered levels of microRNAs. They identified two microRNAs--miR25 and miR93-- whose levels increased in hypoxic tumors.

The team then measured levels of those two microRNAs in the tumors of 148 cancer patients and found that tumors with high levels of miR25 and miR93 led to a worse prognosis in patients compared to tumors with lower levels. The reverse was true for another molecule called cGAS: the lower the level of cGAS in a tumor, the worse the prognosis for the patient.

Previous research has shown that cGAS acts as an alarm for the immune system by detecting mitochondrial DNA floating around the cell--a sign of tissue damage--and activating the body's immune response.

"Given these results, we wondered if these two microRNA molecules, miR25 and miR93, could be lowering cGAS levels to create a protective immunity shield for the tumor," says Min-Zu (Michael) Wu, first author of the paper and a research associate in Salk's Gene Expression Laboratory.

That is exactly what the team confirmed with further experiments. Using mouse models and tissue samples, the researchers found that a low-oxygen (hypoxia) state triggered miR25 and miR93 to set off a chain of cell signaling that ultimately lowered cGAS levels. If the researchers inhibited miR25 and miR93 in tumor cells, then cGAS levels remained high in low-oxygen (hypoxic) tumors.

Researchers could slow tumor growth in mice if they inhibited miR25 and miR93. Yet, in immune-deficient mice, the effect of inhibiting miR25 and miR93 was diminished, further indicating that miR25 and miR93 help promote tumor growth by influencing the immune system.

Identifying miR25 and miR93 may help researchers pinpoint a good target to try to boost cGAS levels and block tumor evasion of the immune response. However, the team says directly targeting microRNA in treatment can be tricky. Targeting the intermediate players in the signaling between the two microRNAs and cGAS may be easier.

"To follow up this study, we're now investigating the different immune cells that can contribute to cancer anti-tumor immunity," adds Wu.

###

Other authors on the paper include Carolyn O'Connor, Wen-Wei Tsai, and Lorena Martin of Salk; Wei-Chung Cheng, Su-Feng Chen and Kou-Juey Wu of the China Medical University, Taichung, Taiwan; Shin Nieh, Chia-Lin Liu, and Yaoh-Shiang Lin of the National Defense Medical Center, Taipei, Taiwan; and Cheng-Jang Wu and Li-Fan Lu of the University of California, San Diego.

Funding was provided by the Razavi Newman Integrative Genomics and Bioinformatics Core Facility, the National Institutes of Health and National Cancer Institute, the Chapman Foundation and the Helmsley Charitable Trust, the G. Harold and Leila Y. Mathers Charitable Foundation, The Leona M. and Harry B. Helmsley Charitable Trust, The Moxie Foundation and UCAM.

About the Salk Institute for Biological Studies:

Every cure has a starting point. The Salk Institute embodies Jonas Salk's mission to dare to make dreams into reality. Its internationally renowned and award-winning scientists explore the very foundations of life, seeking new understandings in neuroscience, genetics, immunology and more. The Institute is an independent nonprofit organization and architectural landmark: small by choice, intimate by nature and fearless in the face of any challenge. Be it cancer or Alzheimer's, aging or diabetes, Salk is where cures begin. Learn more at: salk.edu.

Media Contact

Salk Communications
press@salk.edu
858-453-4100

 @salkinstitute

http://www.salk.edu 

Salk Communications | EurekAlert!

More articles from Life Sciences:

nachricht World’s Largest Study on Allergic Rhinitis Reveals new Risk Genes
17.07.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Plant mothers talk to their embryos via the hormone auxin
17.07.2018 | Institute of Science and Technology Austria

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Microscopic trampoline may help create networks of quantum computers

17.07.2018 | Information Technology

In borophene, boundaries are no barrier

17.07.2018 | Materials Sciences

The role of Sodium for the Enhancement of Solar Cells

17.07.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>