A study led by the Biomedical Research Group on Cancer Marrow Cells of Vall d'Hebron Research Institute (VHIR), from Vall d'Hebron Barcelona Hospital Campus, has allowed two new genes involved in lung cancer to be discovered. The work, which has been published in Cell Death & Disease, opens the door to using the micro ARN miR-99a in the treatment of this pathology.Micro-RNAs regulate the expression of more than 50% of human genes and perform different functions in the body. Micro-RNAs are being studied at a therapeutic level to modulate the expression of genes and, therefore, of proteins that contribute to normal functions and pathological processes such as cancer.In their work, VHIR experts analyzed 47 samples of adenocarcinoma tumour tissue (a type of lung cancer) and of normal tissue of patients at the Vall Hebron University Hospital, and observed that myR-99 was one of the most deregulated micro-RNAs. Thus, they saw that the tumour cells in which miR-99a was more abundant, that is, it was overexpressed, grew less. They also found that the tumour suppressive character of mi-R99a was due to the fact that the cell cycle of the tumour cells was stopped by stimulating the process of apoptosis (cell death).The next step that the researchers considered was to identify the main genes involved in the tumour suppressive character of miR-99a. And they focused on two proteins generated by two genes of the same name largely unexplored until then: E2F2, a transcription factor, and EMR2, a membrane-receptor protein. When the experts overexpressed miR-99a in cell lines, the expression of the two genes diminished. In addition, they found that this lower expression of the genes resulted in a lower protein manufacture. Subsequently, the same results were replicated in mouse models.Another conclusion of the work is that the tumour cells in which miR-99 is overexpressed are less aggressive because they present an epithelial phenotype (or aspect). As explained by Dr. Matilde Lleonart, head of the Biomedical Research Group in Cancer Stem Cells of VHIR, "the 99% of human tumours have origin in the intestinal epithelium, which is made up of distinct cells. In the case of the most aggressive tumours, the tumoral cells go back to a stage of stem cells, in what is known as a 'transition' mesenchyme epithelium' (EMT), what allows them to evolve again and to differentiate them selves into various types of more dangerous tumour cells." In the study, tumour cells that were overexpressing the miR-99a didn't carry out this process, while those without over-expression of this micro RNA did. Specifically, Lleonart adds, "we observed that tumour cells with more miR-99a contained fewer stem cells and these had less biological activity and, therefore, were less aggressive".According to the opinion of Dr. Matilde Lleonart, one of the main practical applications of the work is that "patients with lung tumours that over expresss miR-99a probably require less aggressive therapies, which would allow them to reduce the side effects of treatments. It is estimated that about 10% of patients of lung cancer over express this micro RNA."Lung cancerLung cancer is the most frequent neoplasm worldwide. In addition, it is one of the most aggressive tumours, since only 10% of patients survive five years from diagnosis.VHIRThe VHIR was founded in 1994, and is part of the Vall d'Hebron University Hospital, of the Catalan Health Institute, and is a CERCA center of the Department of Economy and Knowledge of the Generalitat, and is a research institute assigned to the Autonomous University of Barcelona.Vall d'Hebron Barcelona Hospital CampusThe Vall d'Hebron Campus consists of the Vall d'Hebron University Hospital, Vall d'Hebron Research Institute (VHIR), the Vall d'Hebron Institut of Oncology (VHIO) and the Centre for Multiple Sclerosis of Catalonia (Cemcat) The new project represents a new way of working and doing, where research, teaching and clinical practice go together, in the same direction, to join efforts and to grow, being more useful, more productive and more effective.