Significance of microRNA-330/TYMS expression axis through colorectal tumorigenesis

Abstract

Background Colorectal cancer is one of the most common types of cancer worldwide. MiR-330 has been reported as a cell proliferation inhibitor by suppressing thymidylate synthase (TYMS) in FOLFOX, one of the major chemotherapy regimens used to treat colorectal cancers. A number of dysregulated miRNAs have been linked to CRC progression and treatment response and are thought to be promising prognostic biomarkers for this cancer. In the current study, miR-330, TYMS, and their interactions have been investigated in the absence of this chemotherapy to evaluate their therapeutic and diagnostic value for other treatment methods. Material and Methods The expression levels of miR-330 and TYMS were evaluated in-silico using TCGA datasets for colorectal cancer. Data validation was performed on a set of internal samples (100 pairs of CRC tumor specimens and adjacent non-cancerous samples) were determined utilizing RT-qPCR assay. The linkage between clinicopathological parameters and expression levels was also investigated. Results TCGA results illustrated that miR-330 and TYMS are significantly upregulated and downregulated through colorectal tumorigenesis, respectively. QRT-PCR results confirmed that the expression level of miR-330 was significantly higher in tumor tissues relative to margin tissues (p value = 0/0005) whereas TYMS was significantly down-regulated (p value = 0.0001). However, there was no significant association regarding TYMS and patient pathological features while miR-330 expression was associated with tumor stage and lymph node metastases. Conclusion The microRNA-330 inhibited cell proliferation by suppressing thymidylate synthase (TYMS) in colorectal cancer. Therefore, suggesting that they are valuable factors for further studies of alternative treatment and diagnostic methods.