The small non-coding RNA molecule called microRNA-28 has anti-tumor effects against Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) cells, according to a study.
The molecule, which prevents immune-system components known as B-cells from proliferating and promotes their death, could be used to develop treatments against such aggressive lymphomas, researchers said. MicroRNA-28 is also called miR-28.
The study, “miR-28 regulates the germinal center reaction and blocks tumor growth in preclinical models of non-Hodgkin lymphoma,” was published in the journal Blood.
RNA molecules are nucleic acids that facilitate genes’ production of proteins. MicroRNAs regulate gene expression. B-cells are white blood cells that protect the body against infection.
Many aggressive B-cell lymphomas can be treated with current therapies, particularly Adriamycin (doxorubicin)-based chemotherapy combined with Rituxan (rituximab). They are intense treatments that often require hospitalization, however –and the cancer often returns within five years.
“[W]e need to find alternative therapies to replace or complement those that are already available,” Almudena Ramiro, senior author of the study, said in a news release.
Although microRNAs do not code for proteins, they can bind directly to RNA molecules, promoting or inhibiting the expression of certain genes. This mechanism is present in normal cells, but it has also been linked to many cancers.
Ramiro and her team discovered that miR-28 was involved in the regulation of genes responsible for the proliferation, differentiation, and survival of mature B-cells. Because B-cell lymphomas derive from mature B-cells, the researchers wondered whether the microRNA could impact BL and DLBCL cell growth.
They found reduced levels of miR-28 in various B-cell lymphoma subtypes. Loss of the microRNA was associated with malignant transformation of B-cells, they discovered. This suggested that miR-28 could have a tumor suppressor role in the diseases.
The researchers used animal models to force the expression of miR-28 in lymphoma cells, reducing the cells’ ability to grow.
Intravenous administration of artificial miR-28 in animal models also inhibited lymphoma cell proliferation and ultimately promoted cell death, the researchers learned.
“This is particularly relevant for BL and DLBCL, which are often refractory to conventional chemotherapy,” the team wrote. “Taken together, the results of this study reveal the therapeutic potential of miR-28 and provide a rationale for the initiation of clinical trials of miR-28-based therapies to treat B cell [Non-Hodgkin lymphoma].”