AUG 18, 2021 8:11 AM PDT

Insight Into an Antiviral Enzyme That Can Impact Cancer Cells

WRITTEN BY: Carmen Leitch

For many years, researchers have been investigating how a family of enzymes called APOBEC3 can help protect the body from pathogenic viruses, and how it relates to cancer. APOBEC3s are known to prevent some genetic changes, like the insertion of retroelements. Scientists have also found that one enzyme in this family called APOBEC3A can trigger the formation of mutations in the genomes of cancer cells. However, this attack may also cause mutations that increase the growth, metastasis, or drug resistance of cancer cells.

APOBEC3A enzyme (yellow) attacks DNA (white) by promoting the deamination of cytosine (bright orange), which causes genetic mutations in the cell. / Credit: UCI School of Medicine

“In our previous studies, we demonstrated that APOBEC3A-induced DNA mutations are very frequent in cancer patients. In fact, we found they are present in up to 80 percent of certain cancer types such as lung, breast or bladder cancers,” said Rémi Buisson, Ph.D., an assistant professor at the University of California Irvine School of Medicine.  
 
Researchers have now learned more about how APOBEC3A is expressed in tumor cells. Reporting in Nature Communications, the study authors exposed these cells to chemotherapeutic drugs, which can cause genomic damage and an increase in APOBEC3A levels. When cells were infected with viruses, another increase in the level of APOBEC3A was observed. However, this upregulation of APOBEC3A occurred through two totally different mechanisms.

Viral infection stimulates the innate immune system to respond by activating APOBEC3A, which can eliminate the infection. APOBEC enzymes can coax amino groups off of cytosine that change the moleucle to uracil on either single-stranded DNA or RNA, which generates mutations in viral genomes. That can prevent the replication of the virus.

But the chemotherapeutic drugs trigger APOBEC3A through a different pathway, which may also initiate genomic mutations in the cell that makes the cancer more aggressive. Unlike the virally-induced APOBEC3 response, interferons and a molecule called STAT2 are not involved. Instead, the study indicated that the p65/IkBα pathway plays an important role.

“Together, our results reveal different ways for the cells to regulate APOBEC3A expression to address different types of stresses that the cell may encounter,” said Buisson. “By understanding how cancer cells and viral infections regulate APOBEC3A expression, we are poised to take critical step forward toward the development of both new therapeutic strategies to fight cancer and new antiviral therapies.”

This study suggested that additional work will be needed to learn how to prevent the APOBEC3A-caused mutations in DNA so that tumor growth is not increased.

The researchers also noted that it's possible that APOBEC3A activity may contribute to the formation of mutations in viruses like SARS-CoV-2; more research will be needed to learn how APOBEC3A could be influencing the activity, growth, or mutation of viruses.

Sources: AAAS/Eurekalert! via University of California - Irvine, Nature Communications

About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
OCT 01, 2021
Technology
SnapTec® - Single-handed operation for fast and safe sample handling
OCT 01, 2021
SnapTec® - Single-handed operation for fast and safe sample handling
The new Eppendorf Conical Tube SnapTec 50 offers all the advantages of classic conical tubes 50 mL. The decisive, innova ...
OCT 07, 2021
Cancer
Dual Threat: CAR T Cells Modified to Target Two Neuroblastoma Antigens
OCT 07, 2021
Dual Threat: CAR T Cells Modified to Target Two Neuroblastoma Antigens
Neuroblastoma is a cancer of immature nerve cells found in various areas, including the adrenal glands, neck, chest ...
OCT 04, 2021
Cell & Molecular Biology
Studies Reveal Synaptic Disruptions in Schizophrenia
OCT 04, 2021
Studies Reveal Synaptic Disruptions in Schizophrenia
Neurons signal to one another at crucial junctions called synapses, and synaptic dysfunction is thought to play a role i ...
OCT 07, 2021
Neuroscience
Unclogged: Constipation Drug May Stimulate Memory and Cognition
OCT 07, 2021
Unclogged: Constipation Drug May Stimulate Memory and Cognition
A drug commonly prescribed for constipation shows promise for memory and cognition
OCT 17, 2021
Genetics & Genomics
Genes That Cause Disease Seem to Prevent Beneficial Adaptations
OCT 17, 2021
Genes That Cause Disease Seem to Prevent Beneficial Adaptations
A new study has used computational tools to investigate evolution in the human genome that's occurred over the past 50,0 ...
OCT 19, 2021
Cell & Molecular Biology
Mouse Fathers Passed Immunity Onto Offpsring After Infection
OCT 19, 2021
Mouse Fathers Passed Immunity Onto Offpsring After Infection
Parents pass their genes on to their children. But they can pass down other things too with epigenetic marks, chemical t ...
Loading Comments...