BCL-۲, IRS-۱, AKT-۳, PTEN, Survivin and HIF-۱A expression level in non-small cell lung cancer patients

Background Lung cancer continues to be the foremost cause of cancer-related deaths worldwide, highlighting the pressing need for novel therapeutic approaches. MicroRNAs (miRNAs) are small, non-coding RNA molecules that are crucial in regulating gene expression and are involved in various cellular functions such as proliferation, apoptosis, invasion, and metastasis. Their capacity to target multiple genes at the mRNA level positions them as significant contributors to cancer biology. Methods In this research, we utilized a range of bioinformatics tools to identify and validate target genes for specific miRNAs linked to non-small-cell lung cancer (NSCLC). We employed tools including TargetScan, miRDIP, miRmap, and miRanda to assess potential target genes. Subsequently, STRING, GeneMANIA, and TRED were used to predict interactions and functional relationships among these genes. The expression levels of selected target genes were quantified in NSCLC tumor tissues and adjacent normal tissues through SYBR Green qRT-PCR. Results Our analysis identified BCL۲ and AKT۳ as target genes for miR-۱۵/۱۶. Notably, BCL۲ showed a significant negative correlation with the expression levels of miR-۱۵a. Additionally, statistical analysis indicated a significant relationship between BCL۲ expression and disease stage (p-value = ۰.۰۴), suggesting its potential as a prognostic marker. We also confirmed PTEN as a validated target gene of miR-۲۱, which exhibited a substantial reduction in expression in tumor tissues compared to adjacent normal tissues. IRS۱ was recognized as a target gene for both miR-۱۲۶ and miR-۱۲۸; our results revealed a significant negative correlation between IRS۱ expression levels and these two miRNAs. In contrast, we found a positive correlation between miR-۲۱۰ and HIF۱A at the mRNA level. Conclusion In summary, our findings indicate that restoring the expression of miR-۱۵/۱۶, miR-۱۲۶, and miR-۱۲۸ may represent promising therapeutic strategies for NSCLC by modulating critical pathways involved in cell proliferation and apoptosis. These insights not only deepen our understanding of the molecular mechanisms underlying NSCLC but also lay the groundwork for developing targeted therapies aimed at improving patient outcomes. Future research should concentrate on validating these findings in larger patient cohorts and investigating the clinical therapeutic potential of these miRNAs.

کلیدواژه ها:

Gene target ، miRNAs ، non-small-cell lung cancer