Abstract
Abstract
Background
The aim of the study was to determine the exonic and 3'UTR sequences of EGFR, PIK3CA and KRAS genes in 39 sporadic lung cancer tumors and to reveal the relationship between the changes in the miRNA binding profile of tumors with somatic variation in the 3'UTR region and the metastatic status of the tumors.
Methods
The exonic and 3'UTR sequences of three genes in 39 sporadic lung carcinoma tumors were extracted by next generation sequencing. In tumors with somatic variation in the 3'UTR region, the changes caused by the variation in the miRNA binding profile were determined by bioinformatic analysis. The expression profile of miRNAs in lung cancer and other solid tumors compared to normal tissue was determined. Pathway analysis was performed to determine which signaling pathways are affected by miRNAs that differ depending on variation.
Results
A statistically significant correlation was found between the presence of miRNA that could not bind to the 3'UTR region due to variation in at least one of the EGFR or KRAS genes and the presence of metastasis in the tumor. It was revealed that variations in the 3'UTR regions of EGFR and KRAS oncogenes may be associated with the mechanism of metastasis and drug resistance as a result of their ability to cause increased expression of these oncogenes by preventing the binding of some miRNAs.
Conclusion
In this study, hsa-miR-124-3p, hsa-miR-506-3p, hsa-miR-1290 and hsa-miR-6514-3p were found to be particularly prominent in lung carcinoma in relation to these biological pathways.
Publisher
Research Square Platform LLC