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A microRNA known as miR-181a dampens signals from the NF-κB pathway and affects the pathogenesis of diffuse large B-cell lymphoma (DLBCL), according to research published in Blood.
The study showed that, by reducing NF-κB signaling, miR-181a hinders tumor cell proliferation and survival.
And the effect is more pronounced in activated B-cell-like (ABC) DLBCL than in germinal center B-cell-like (GCB) DLBCL.
The researchers therefore believe miR-181a could be used to treat ABC DLBCL.
“The miR-181a microRNA is one of the first examples of a pathway that deactivates NF-κB at multiple levels, functioning as a master regulator,” said study author Izidore S. Lossos, MD, of the University of Miami Miller School of Medicine in Florida.
“In certain tumors, there is no expression of this microRNA, which allows cells to propagate. We believe miR-181a could eventually be used
therapeutically.”
To understand the role of miR-181a in the different types of DLBCL, Dr Lossos and his colleaguese studied both cell lines and mouse models.
The team found that miR-181a levels were significantly lower in ABC DLBCL than in GCB DLBCL.
When they increased miR-181a expression in DLBCL cell lines, the researchers observed a reduction in NF-κB activity and a decrease in cell proliferation and survival. These effects were more potent in ABC DLBCL than in GCB DLBCL.
When the researchers increased miR-181a expression in the mouse models, they observed a significant reduction in tumor growth and a significant increase in animal survival, but only in ABC DLBCL. In GCB DLBCL, there were no significant changes compared to controls.
The researchers said the ability of miR-181a to reduce NF-κB levels may be why the presence of miR-181a has been linked to better outcomes for certain DLBCL patients. Previous studies by Dr Lossos’s group have shown that DLBCL patients whose tumors contain more miR-181a have better prognoses.
With the current study, the team found that miR-181a is a master regulator, turning off a number of genes in the NF-κB pathway, including CARD11, a known DLBCL oncogene, and a number of transcription factors that drive NF-κB signaling.
“We knew that miR181a was biomarker for survival,” Dr Lossos said. “This explains the mechanisms behind it.”
In addition to providing a better understanding of the NF-κB pathway, these results provide hope that miR-181a could be used to improve treatment for patients with ABC DLBCL.
“We are trying to develop miR-181a as a potential therapy,” Dr Lossos said. “But we are only at the beginning. Much more work needs to be done. It will not be a simple journey, but we are sure it can be done and tested in humans eventually to see that it indeed will improve patients’ outcomes.” 
A microRNA known as miR-181a dampens signals from the NF-κB pathway and affects the pathogenesis of diffuse large B-cell lymphoma (DLBCL), according to research published in Blood.
The study showed that, by reducing NF-κB signaling, miR-181a hinders tumor cell proliferation and survival.
And the effect is more pronounced in activated B-cell-like (ABC) DLBCL than in germinal center B-cell-like (GCB) DLBCL.
The researchers therefore believe miR-181a could be used to treat ABC DLBCL.
“The miR-181a microRNA is one of the first examples of a pathway that deactivates NF-κB at multiple levels, functioning as a master regulator,” said study author Izidore S. Lossos, MD, of the University of Miami Miller School of Medicine in Florida.
“In certain tumors, there is no expression of this microRNA, which allows cells to propagate. We believe miR-181a could eventually be used
therapeutically.”
To understand the role of miR-181a in the different types of DLBCL, Dr Lossos and his colleaguese studied both cell lines and mouse models.
The team found that miR-181a levels were significantly lower in ABC DLBCL than in GCB DLBCL.
When they increased miR-181a expression in DLBCL cell lines, the researchers observed a reduction in NF-κB activity and a decrease in cell proliferation and survival. These effects were more potent in ABC DLBCL than in GCB DLBCL.
When the researchers increased miR-181a expression in the mouse models, they observed a significant reduction in tumor growth and a significant increase in animal survival, but only in ABC DLBCL. In GCB DLBCL, there were no significant changes compared to controls.
The researchers said the ability of miR-181a to reduce NF-κB levels may be why the presence of miR-181a has been linked to better outcomes for certain DLBCL patients. Previous studies by Dr Lossos’s group have shown that DLBCL patients whose tumors contain more miR-181a have better prognoses.
With the current study, the team found that miR-181a is a master regulator, turning off a number of genes in the NF-κB pathway, including CARD11, a known DLBCL oncogene, and a number of transcription factors that drive NF-κB signaling.
“We knew that miR181a was biomarker for survival,” Dr Lossos said. “This explains the mechanisms behind it.”
In addition to providing a better understanding of the NF-κB pathway, these results provide hope that miR-181a could be used to improve treatment for patients with ABC DLBCL.
“We are trying to develop miR-181a as a potential therapy,” Dr Lossos said. “But we are only at the beginning. Much more work needs to be done. It will not be a simple journey, but we are sure it can be done and tested in humans eventually to see that it indeed will improve patients’ outcomes.”
A microRNA known as miR-181a dampens signals from the NF-κB pathway and affects the pathogenesis of diffuse large B-cell lymphoma (DLBCL), according to research published in Blood.
The study showed that, by reducing NF-κB signaling, miR-181a hinders tumor cell proliferation and survival.
And the effect is more pronounced in activated B-cell-like (ABC) DLBCL than in germinal center B-cell-like (GCB) DLBCL.
The researchers therefore believe miR-181a could be used to treat ABC DLBCL.
“The miR-181a microRNA is one of the first examples of a pathway that deactivates NF-κB at multiple levels, functioning as a master regulator,” said study author Izidore S. Lossos, MD, of the University of Miami Miller School of Medicine in Florida.
“In certain tumors, there is no expression of this microRNA, which allows cells to propagate. We believe miR-181a could eventually be used
therapeutically.”
To understand the role of miR-181a in the different types of DLBCL, Dr Lossos and his colleaguese studied both cell lines and mouse models.
The team found that miR-181a levels were significantly lower in ABC DLBCL than in GCB DLBCL.
When they increased miR-181a expression in DLBCL cell lines, the researchers observed a reduction in NF-κB activity and a decrease in cell proliferation and survival. These effects were more potent in ABC DLBCL than in GCB DLBCL.
When the researchers increased miR-181a expression in the mouse models, they observed a significant reduction in tumor growth and a significant increase in animal survival, but only in ABC DLBCL. In GCB DLBCL, there were no significant changes compared to controls.
The researchers said the ability of miR-181a to reduce NF-κB levels may be why the presence of miR-181a has been linked to better outcomes for certain DLBCL patients. Previous studies by Dr Lossos’s group have shown that DLBCL patients whose tumors contain more miR-181a have better prognoses.
With the current study, the team found that miR-181a is a master regulator, turning off a number of genes in the NF-κB pathway, including CARD11, a known DLBCL oncogene, and a number of transcription factors that drive NF-κB signaling.
“We knew that miR181a was biomarker for survival,” Dr Lossos said. “This explains the mechanisms behind it.”
In addition to providing a better understanding of the NF-κB pathway, these results provide hope that miR-181a could be used to improve treatment for patients with ABC DLBCL.
“We are trying to develop miR-181a as a potential therapy,” Dr Lossos said. “But we are only at the beginning. Much more work needs to be done. It will not be a simple journey, but we are sure it can be done and tested in humans eventually to see that it indeed will improve patients’ outcomes.”