Study reveals the mechanisms of how let-7 is inhibited in neuroblastoma
Neuroblastoma is a common malignant tumor in infancy and childhood. Although the development of treatment is enormous, the cancer is still deadly in some cases. Most of the survivors have long-term effects from the treatment.
Now, scientists from Dana-Farber/Boston Children's Cancer and Blood Disorders Center have discovered that let-7, which is a microRNA, helps to prevent neuroblastoma. This finding could lead to the development of novel targeted treatment.
Previous studies mainly looked at the genes that encode proteins, not microRNAs. The let-7 family of microRNAs play a role in stem-cell differentiation, and act as a tumor suppressor. There is evidence that the LIN28B protein is involved in neuroblastoma. LIN28B is known to suppress the production of let-7.
In the latest research, the scientists investigated neuroblastoma cells and analyzed data of patients with the cancer. They discovered that there are other pathways that suppress let-7.
John Powers, the first author of the paper, noted that let-7 inhibition is crucial for the progression of neuroblastoma. In neuroblastoma, there are actually three or more mechanisms for eliminating let-7.
The research team found that in approximately 25 percent of patients, the oncogene MYCN is amplified. A lot of MYCN mRNA is produced, making neuroblastoma able to sequester let-7. These patients tend to have the worst outcomes.
In addition, other patients often lose let-7 through chromosomal deletions. This genetic loss of let-7 is also associated with poor prognosis.
Furthermore, patients with MYCN amplification rarely have chromosomal loss of let-7. The study indicated that most neuroblastomas suppress let-7 through a single mechanism.
Based on these findings, Powers suggested that restoring let-7 might be a way to treat neuroblastoma. This could also have implications for other types of cancers that lack let-7. Let-7 might be used as a novel therapy, but further investigation is needed.