MicroRNAs affecting epithelial-mesenchymal transition pathway in malignant mesothelioma

Background: Malignant mesothelioma is a fatal cancer of the mesothelial cells characterized by previous exposure to asbestos, long latency period and shorter survival time thereafter. Lack of highly sensitive and specific biomarkers and no curative treatment at present has made the continuous study of mesothelioma important. One of the biomarker under study are the microRNAs (miRNAs) which are small non-coding RNAs of about 20-22 nucleotides long which regulate post-translational gene expression. MiRNAs control several essential biological pathways including the epithelial-mesenchymal transition (EMT) pathway. Their dysregulation can lead to disruption of these pathways and also to the development of cancer. Identifying and understanding the role played by these miRNAs in malignant mesothelioma will help in their development as an effective diagnostic, prognostic and therapeutic target for this cancer. Aims: The study aims to first identify miRNAs previously linked with malignant mesothelioma, invasion and the EMT pathway based on review of literature. The study then aims to characterize miRNAs expression in established mesothelial cell lines used widely in mesothelioma research. Material & methods: Literature review is conducted using peer reviewed articles and limiting the articles published within the last 5 years. For characterizing the miRNAs, 6 mesothelial cell lines are used of which one is non-tumorigenic and used to represent a healthy control. Small RNA sequencing is done of all 6 cell lines and results analyzed using the Chipster analysis software. Results: A comprehensive list of 100 miRNAs was created which were linked to malignant mesothelioma, invasion, metastasis and EMT pathway. Small RNA sequencing of the cell lines revealed 134 miRNAs which were expressed in at least one of the cell lines. 34 of these miRNAs had higher counts in the healthy control as compared to all the cancer cell lines. In addition, we found 19 miRNAs having low counts in the control cell line but showed downregulation to zero in all the cancer cell lines. 4 miRNAs, namely miR-10a-5p, miR- 21-5p, miR-23b-3p and miR-183-5p, were also found in this study which were not previously linked with malignant mesothelioma. Conclusion: Characterization of the available mesothelial cell lines is the first step in understanding the role played by miRNAs in the development of this cancer. Further studies are needed to confirm the entire list of mesothelioma associated miRNAs found here, especially the 4 miRNAs which were not previously linked to mesothelioma. Validation of the miRNAs through comparison with patient samples with higher number of biological replicates and greater depth of libraries along with miRNA pathway analysis will help the development of miRNAs as a diagnostic and prognostic marker for this cancer