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

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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.

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References

  1. Bray F, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.

  2. Sideris M, Papagrigoriadis S. Molecular biomarkers and classification models in the evaluation of the prognosis of colorectal cancer. Anticancer Res. 2014;34(5):2061–8.

    CAS  PubMed  Google Scholar 

  3. Arnold M, et al. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017;66(4):683–91.

    Article  PubMed  Google Scholar 

  4. Azar MRMH, et al. Dysregulation of miR-27a and SMAD2 can be a reliable indicator in the prognosis and diagnosis of CRC as well as in response to chemotherapy drugs. Gene Rep. 2020;21:100844.

  5. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30.

    Article  PubMed  Google Scholar 

  6. Siegel RL, et al. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020;70(3):145–64.

  7. De Rosa M, et al. Genetics, diagnosis and management of colorectal cancer. Oncol Rep. 2015;34(3):1087–96.

    Article  PubMed  Google Scholar 

  8. Akbari M, et al. CD133: an emerging prognostic factor and therapeutic target in colorectal cancer. Cell Biol Int. 2020;44(2):368–80.

    Article  PubMed  Google Scholar 

  9. Newton K, Newman W, Hill J. Review of biomarkers in colorectal cancer. Colorectal Dis. 2012;14(1):3–17.

    Article  CAS  PubMed  Google Scholar 

  10. Asadi M, et al. Transcript level of microRNA processing elements in gastric cancer. J Gastrointest Cancer. 2019;50(4):855–9.

    Article  CAS  PubMed  Google Scholar 

  11. Shirafkan N, et al. MicroRNAs as novel biomarkers for colorectal cancer: new outlooks. Biomed Pharmacother. 2018;97:1319–30.

    Article  CAS  PubMed  Google Scholar 

  12. Ghasabi M, et al. The effect of combined miR-200c replacement and cisplatin on apoptosis induction and inhibition of gastric cancer cell line migration. J Cell Physiol. 2019;234(12):22581–92.

    Article  CAS  PubMed  Google Scholar 

  13. Shomali N, et al. Downregulation of miR-146a promotes cell migration in Helicobacter pylori–negative gastric cancer. J Cell Biochem. 2019;120(6):9495–505.

    Article  CAS  PubMed  Google Scholar 

  14. Ding L, et al. The dual role of microRNAs in colorectal cancer progression. Int J Mol Sci. 2018;19(9):2791.

    Article  PubMed Central  Google Scholar 

  15. Sadeghiyeh N, et al. MicroRNA-145 replacement effect on growth and migration inhibition in lung cancer cell line. Biomed Pharmacother. 2019;111:460–7.

    Article  CAS  PubMed  Google Scholar 

  16. Sehati N, et al. MicroRNA-330 inhibits growth and migration of melanoma A375 cells: In vitro study. J Cell Biochem. 2020;121(1):458–67.

    Article  CAS  PubMed  Google Scholar 

  17. Tamjidifar R, et al. Prognostic and diagnostic values of miR-506 and SPON 1 in colorectal cancer with clinicopathological considerations. J Gastrointest Cancer. 2020:1–5.

  18. O’Leary NA, et al. Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation. Nucleic Acids Res. 2016;44(D1):D733–45.

    Article  CAS  PubMed  Google Scholar 

  19. Shirjang S, et al. miR-330 regulates colorectal cancer oncogenesis by targeting BACH1. Adv Pharm Bull. 2020;10(3):444–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lee KH, et al. MicroRNA-330 acts as tumor suppressor and induces apoptosis of prostate cancer cells through E2F1-mediated suppression of Akt phosphorylation. Oncogene. 2009;28(38):3360–70.

    Article  CAS  PubMed  Google Scholar 

  21. Qu S, et al. MicroRNA-330 is an oncogenic factor in glioblastoma cells by regulating SH3GL2 gene. PLoS One. 2012;7(9)e46010.

  22. Yoo H-I, Kim B-K, Yoon SK. MicroRNA-330-5p negatively regulates ITGA5 expression in human colorectal cancer. Oncol Rep. 2016;36(5):3023–9.

    Article  CAS  PubMed  Google Scholar 

  23. Xu W, et al. MicroRNA-330 inhibited cell proliferation and enhanced chemosensitivity to 5-fluorouracil in colorectal cancer by directly targeting thymidylate synthase. Oncol Lett. 2017;13(5):3387–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Soheilifar MH, et al. BMI1 as a potential target of miR-330–3p in colorectal cancer. Middle East J Rehabil Health Stud. 2018:1–6.

  25. Li Y, et al. miR-330 regulates the proliferation of colorectal cancer cells by targeting Cdc42. Biochem Biophys Res Commun. 2013;431(3):560–5.

    Article  CAS  PubMed  Google Scholar 

  26. Mansoori B, et al. miR-330 suppresses EMT and induces apoptosis by downregulating HMGA2 in human colorectal cancer. J Cell Physiol. 2020;235(2):920–31.

    Article  CAS  PubMed  Google Scholar 

  27. Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003;3(5):330–8.

    Article  CAS  PubMed  Google Scholar 

  28. Escalante PI, Quiñones LA, Contreras HR. Epithelial-mesenchymal transition and microRNAs in colorectal cancer chemoresistance to FOLFOX. Pharmaceutics. 2021;13(1):75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Gallegos-Arreola MP, et al. TYMS 2R3R polymorphism and DPYD [IVS] 14+ 1G> A mutation genes in Mexican colorectal cancer patients. Acta Biochim Pol. 2018;65(2):227–34.

    Article  CAS  PubMed  Google Scholar 

  30. Carreras CW, Santi DV. The catalytic mechanism and structure of thymidylate synthase. Annu Rev Biochem. 1995;64(1):721–62.

    Article  CAS  PubMed  Google Scholar 

  31. Jiang H, et al. Expression of ERCC1 and TYMS in colorectal cancer patients and the predictive value of chemotherapy efficacy. Oncol Lett. 2019;18(2):1157–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Popat S, Matakidou A, Houlston RS. Thymidylate synthase expression and prognosis in colorectal cancer: a systematic review and meta-analysis. J Clin Oncol. 2004;22(3):529–36.

    Article  CAS  PubMed  Google Scholar 

  33. Koumarianou A, et al. Prognostic markers in early-stage colorectal cancer: significance of TYMS mRNA expression. Anticancer Res. 2014;34(9):4949–62.

  34. Klingbiel D, et al. Thymidylate synthase (TS) expression as a prognostic molecular marker in stage II/III colon cancer. Proc Am Soc Clin Oncol. 2013.

  35. Amin MB, Edge SB. AJCC cancer staging manual. Springer; 2017.

  36. Guo S, et al. SH3PXD2A-AS1/miR-330–5p/UBA2 ceRNA network mediates the progression of colorectal cancer through regulating the activity of the Wnt/β-catenin signaling pathway. Environ Toxicol. 2020.

  37. Asadi M, et al. Identification of miRNAs correlating with stage and progression of colorectal cancer. Colorectal Cancer. 2019;8(2):CRC06.

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Acknowledgements

The authors are thankful to patients and their families for their contribution to the study.

Funding

This study was supported by a grant from the research deputy of the Department of Tuberculosis and Lung Diseases Research Center, University Tabriz University of Medical Sciences, Tabriz, Iran.

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Authors and Affiliations

  1. Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Leila Karimi, Milad Jaberi, Habib Zarredar, Venus Zafari & Soghra Bornehdeli

  2. Department of Basic Oncology, Health Institute of Ege University, Izmir, Turkey

    Milad Asadi

  3. Department of General Surgery, Sina Hospital, Tabriz University of Medical Sciences, Tabriz, Iran

    Saman Niknam

  4. Department of General Surgery, School of Medicine, Imam Reza Hospital, Tabriz University of Medical Sciences, P.O. Box: 5175971583, Tabriz, Iran

    Touraj Asvadi Kermani

Authors
  1. Leila Karimi
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  2. Milad Jaberi
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  3. Milad Asadi
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  4. Habib Zarredar
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  5. Venus Zafari
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  6. Soghra Bornehdeli
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  7. Saman Niknam
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  8. Touraj Asvadi Kermani
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Contributions

(I). Conception and design: Leila Karimiand Touraj Asvadi Kermani. (II). Administrative support: Milad Jaberi. (III). Provision of study materials or patients: Milad Asadi. (IV). Collection and assembly of data: Habib Zarredar and Venus Zafari. (V). Data analysis and interpretation: Milad Asadi and Soghra Bornehdeli. (VI). Manuscript writing: Leila Karimi. (VII). Final approval of manuscript: all authors.

Corresponding author

Correspondence to Touraj Asvadi Kermani.

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Ethics Approval and Consent to Participate

This study was confirmed by the Ethical Committee of Tabriz University of Medical Sciences (IR.TBZMED.REC.1399.206) and written informed consent was obtained from all patients.

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Written informed consent was obtained from all patients.

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The authors declare no competing interests.

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Karimi, L., Jaberi, M., Asadi, M. et al. Significance of microRNA-330-5p/TYMS Expression Axis in the Pathogenesis of Colorectal Tumorigenesis. J Gastrointest Canc 53, 965–970 (2022). https://doi.org/10.1007/s12029-021-00695-x

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  • DOI: https://doi.org/10.1007/s12029-021-00695-x

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