Two small non-coding RNA molecules — miR-146a and miR-146b — appear to protect against the development of blood cancers such as B-cell lymphoma and acute myeloid leukemia, a mouse study suggests.
These molecules, however, work in slightly different ways, and researchers hope their findings will help shed some light on the mechanisms that lead to different types of lymphoma and leukemia in humans.
The study, “Ablation of miR-146b in mice causes hematopoietic malignancy,” was published in the journal Blood Advances.
MicroRNAs (miRNAs) are small non-coding RNAs with a regulatory function in the body, preventing certain genes from generating a protein. These tiny molecules can take part in a multitude of biological processes, including inflammation, cell differentiation, cell growth, and tumor progression.
A particular miRNA called miR-146a may have a role in suppressing the development of blood malignancies. Mice without this molecule tend to have autoimmune-mediated inflammation, and develop spontaneous lymphomas and leukemias as they age.
Another molecule that is very similar structurally to miR-146a — miR-146b — also seems to prevent against several cancers, including breast, brain, and gallbladder cancers. However, its role in blood cancers and how it differs from miR-146a has not been fully evaluated.
To take a closer look at this, researchers at the Tokyo Medical and Dental University (TMDU) developed genetically modified mice that lacked either the miR-146a or miR-146b molecules.
“This allowed us to see if the effects of lacking miR-146a differed from those for miR-146b, and also to compare these mice to those without any knockout at all. We could also detect any similarities in their cancers to those that develop in humans,” Hiroshi Asahara, MD, PhD, a researcher at the department of systems biomedicine of TMDU and senior author of the study, said in a press release.
The loss of these miRNAs caused both animal models to develop blood cancers, including B-cell lymphoma and acute myeloid leukemia, later in life.
However, the diseases were slightly different between the two groups, with mice lacking miR-146b showing features of a low-grade follicular lymphoma, and mice without miR-146a having a more aggressive disease, such as high-grade follicular lymphoma and diffuse large B-cell lymphoma.
Consistent with the findings, the researchers found that B-cells lacking these molecules produced higher amounts of a signaling molecule called NF-κB — key in lymphoma development — which made them proliferate faster than normal B-cells. However, cells without miR-146a made more of this molecule, explaining why mice without miR-146a had more aggressive cancers.
These findings demonstrate that miR-146b, similar to miR-146a, may contribute to the development of blood malignancies. However, studies suggest that miR-146b may be involved in the development of cancers when miR-146b is lacking.
Additional studies are now warranted to explore if “genetic alteration of miR-146b in humans could be associated with lymphatic or myeloid disease,” the researchers wrote. They expect that these results may help better understand the role of microRNAs in human cancer.
