Significance of microRNA-330-5p/TYMS Expression Axis in the Pathogenesis of Colorectal Tumorigenesis

J Gastrointest Cancer. 2022 Dec;53(4):965-970. doi: 10.1007/s12029-021-00695-x. Epub 2021 Oct 14.

Abstract

Background: Colorectal cancer (CRC) is one of the most common types of cancer worldwide. A number of dysregulated microRNAs (miRNAs) have been linked to CRC progression and treatment response and are thought to be promising prognostic biomarkers for this cancer. microRNA-330 (miR-330-5p) has been reported to inhibit cell proliferation through suppressing thymidylate synthase (TYMS). In the current study, miR-330-5p, TYMS, and their interactions were investigated to evaluate their therapeutic and diagnostic value for CRC treatment.

Methods: The expression levels of miR-330-5p and TYMS were evaluated in silico using TCGA datasets for CRC. Data validation was performed on a set of internal samples (100 pairs of CRC tumor specimens and adjacent non-cancerous samples) utilizing real-time PCR assay. The linkage between clinicopathological parameters and expression levels was also investigated.

Results: TCGA results indicated that miR-330-5p and TYMS were significantly upregulated and downregulated in the CRC, respectively. Real-time PCR results confirmed that the expression of miR-330-5p was significantly upregulated in tumor tissues relative to marginal tissues (P = 0.0005), whereas TYMS expression was significantly downregulated (P = 0.0001). The transcript level of miR-330-5p 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.

Keywords: Colorectal cancer; MicroRNA; Prognosis; TYMS; miR-330-5p.

MeSH terms

  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Transformation, Neoplastic
  • Colorectal Neoplasms* / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Thymidylate Synthase / genetics
  • Thymidylate Synthase / metabolism

Substances

  • Thymidylate Synthase
  • MicroRNAs
  • TYMS protein, human
  • MIRN330 microRNA, human