A recent study published in the current issue of the journal Human Molecular Genetics provided a better understanding of the molecular alterations during lung cancer development.
The study titled “Expression inactivation of SMARCA4 by microRNAs in lung tumors,” a research team from the University of Granada” was developed in partnership with the universities of Harvard and Yale, and found that microRNAs can neutralize the function of SMARCA4, a gene that protects healthy cells from developing into cancer cells.
Somatic Mutations in SMARCA4 have been identified in lung cancer cell lines. While somatic mutations have been detected in a small subset of lung primary tumors, about one-third of lung cancer cell lines of non-small-cell lung cancer (NSCLC) harbor inactivating SMARCA4 somatic mutations.
In the study, researchers found that SMARCA4 expression is regulated specifically by miR-155 through binding to two alternative coding patterns. The experiments indicate that the oncogenic properties of miR-155 in lung cancer can be largely explained by its role in SMARCA4 inhibition.
This newly discovered functional relationship could explain the poor prognosis displayed by patients with lung cancer that have independent high miR-155 and low SMARCA4 expression levels. The results were consolidated in pre-clinical mice models and may lead to applications of miRNA technology for diagnosis and prognosis of lung cancer.
“We had previously discovered that lung tumours in patients lost the activity of the SMARCA4 gene, which carries out tasks that protect normal cells from turning into tumour cells. This new research proves that this loss in the tumour-suppression activity of SMARCA4 could be attributed to the activity of certain microRNAs,” said Professor Pedro P. Medina, the principal investigator in this project and a researcher at the Molecular Biochemistry and Biology I Department at the University of Granada in a recent news release.
“This result has opened up a new research line in our lab, by means of which we aim to explore new therapeutic pathways based on the regulation conducted by microRNAs,” he added in the news release.