Genetic Variation in MiRNA Processing Machinery Genes and Susceptibility to Colorectal Cancer in the Iranian Population
-
Marzieh Mobaraki
,
Hamid Asadzadeh Aghdaei
,
Seyed Abdolhamid Angaji
,
Ehsan Nazem Alhosseini-Mojarad
,
Sedigheh Arbabian
Abstract
Background: We aimed to elucidate the potential correlation between single-nucleotide polymorphisms (SNPs) in miRNA machinery genes and colorectal cancer (CRC) risk in an Iranian cohort.
Methods: We conducted a robust case‒control study involving 507 participants, which included 213 patients diagnosed with CRC and 294 healthy controls at Research Institute for Gastroenterology and Liver Diseases in Tehran Province, Iran in 2018. The study focused on genotyping four specific SNPs, RAN (rs14035), GEMIN3 (rs197412), GEMIN4 (rs2740348), and Dicer (rs3742330), using advanced ARMS-PCR and Tetra-primer ARMS-PCR techniques.
Results: Notably, our investigation revealed the significant inverse association between the C/C genotype of rs197412 in the GEMIN3 gene and CRC risk (OR=0.54, 95% CI=0.33-0.87; P=0.0087). In stark contrast, the T/T genotype of rs14035 in the RAN gene was strongly associated with a heightened risk of developing CRC (OR=4.44, 95% CI=2.60-7.57, P<0.0001). Furthermore, we found that the G/G genotype of rs2740348 in GEMIN4 posed an increased risk for CRC (OR=2.9, 95% CI=1.44-5.85, P=0.0041) and it has a major effect on CRC risk in our population. The alleles and genotypes of rs3742330 in Dicer, however, did not exhibit a significant correlation with CRC.
Conclusion: Our study provides compelling evidence that SNPs within miRNA processing genes significantly contribute to susceptibility to CRC among the Iranian population. Our research not only contributes to the growing body of miRNA-related genetic studies but also opens avenues for population-specific risk assessment and personalized medicine approaches in cancer therapy.
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28. Li Y, Zhang F, Xing C (2020). A Systematic Review and Meta‐Analysis for the Association of Gene Polymorphisms in RAN with Cancer Risk. Dis Markers, 2020:9026707.
29. Gautam A (2022). DNA and RNA Isolation Techniques for Non-experts. ed. Springer.
30. Ye S, Dhillon S, Ke X, et al (2001). An efficient procedure for genotyping single nucleotide polymorphisms. Nucleic Acids Res, 29 (17):E88-8.
31. Bologna NG, Schapire AL, Palatnik JF (2013). Processing of plant microRNA precursors. Brief Funct Genomics, 12 (1):37-45.
32. Wang X, Li D, Sun L, et al (2020). Regulation of the small GTPase Ran by miR-802 modulates proliferation and metastasis in colorectal cancer cells. Br J Cancer, 122 (11):1695-1706.
33. Shao Y, Shen Y, Zhao L, et al (2020). Association of microRNA biosynthesis genes XPO5 and RAN polymorphisms with cancer susceptibility: Bayesian hierarchical meta-analysis. J Cancer, 11 (8):2181-2191.
34. Osuch-Wojcikiewicz E, Bruzgielewicz A, Niemczyk K, et al (2015). Association of polymorphic variants of miRNA processing genes with larynx cancer risk in a polish population. Biomed Res Int, 2015:298378.
35. Zhang C, Sun C, Zhao Y, et al (2022). Overview of MicroRNAs as diagnostic and prognostic biomarkers for high-incidence cancers in 2021. Int J Mol Sci, 23 (19):11389.
36. Zhao Y, Du Y, Zhao S, Guo Z (2015). Single-nucleotide polymorphisms of microRNA processing machinery genes and risk of colorectal cancer. Onco Targets Ther, 8:421-425.
37. Luan N, Mu Y, Mu J, et al (2021). Dicer1 promotes colon cancer cell invasion and migration through modulation of tRF-20-MEJB5Y13 expression under hypoxia. Front Genet, 12:638244.
2. Bhurgri H, Samiullah S (2017). Colon cancer screening--is it time yet? J Coll Physicians Surg Pak, 27(6):327-328.
3. Maajani K, Khodadost M, Fattahi A, et al (2019). Survival rate of colorectal cancer in Iran: a systematic review and meta-analysis. Asian Pac J Cancer Prev, 20 (1):13-21.
4. Alidoust M, Hamzehzadeh L, Rivandi M, Pasdar A (2018). Polymorphisms in non-coding RNAs and risk of colorectal cancer: A systematic review and meta-analysis. Crit Rev Oncol Hematol, 132:100-110.
5. Jiang H, Ge F, Hu B, Wu L, Yang H, Wang H (2017). rs35301225 polymorphism in miR-34a promotes development of human colon cancer by deregulation of 3′ UTR in E2F1 in Chinese population. Cancer Cell Int, 17:39.
6. O'Brien J, Hayder H, Zayed Y, Peng C (2018). Overview of microRNA biogenesis, mechanisms of actions, and circulation. Front Endocrinol (Lausanne), 9:402.
7. Annese T, Tamma R, De Giorgis M, Ribatti D (2020). microRNAs biogenesis, functions and role in tumor angiogenesis. Front Oncol, 10:581007.
8. Tishkoff SA, Campbell MC, Rawlings-Goss RA (2014). Global population-specific variation in miRNA associated with cancer risk and clinical biomarkers. BMC Med Genomics, 7:53.
9. Wilson RC, Tambe A, Kidwell MA, et al (2015). Dicer-TRBP complex formation ensures accurate mammalian microRNA biogenesis. Mol Cell, 57 (3):397-407.
10. Boni V, Zarate R, Villa J, et al (2011). Role of primary miRNA polymorphic variants in metastatic colon cancer patients treated with 5-fluorouracil and irinotecan. Pharmacogenomics J, 11(6):429-36.
11. Guenter J, Abadi S, Lim H, et al (2021). Evaluating genomic biomarkers associated with resistance or sensitivity to chemotherapy in patients with advanced breast and colorectal cancer. J Oncol Pharm Pract, 27 (6):1371-1381.
12. Peters U, Jiao S, Schumacher F, et al (2013). Colon cancer family registry and the genetics and epidemiology of colorectal cancer Consortium. Identification of genetic susceptibility loci for colorectal tumors in a genome-wide meta-analysis. Gastroenterology, 144(4):799-807.e24.
13. Ali Syeda Z, Langden SSS, Munkhzul C, et al(2020). Regulatory mechanism of MicroRNA expression in cancer. Int J Mol Sci, 21 (5):1723.
14. Gluud M, Willerslev-Olsen A, Gjerdrum LMR, et al (2020). MicroRNAs in the pathogenesis, diagnosis, prognosis and targeted treatment of cutaneous T-cell lymphomas. Cancers (Basel), 12 (5):1229.
15. Linck-Paulus L, Hellerbrand C, Bosserhoff AK, Dietrich P (2020). Dissimilar appearances are deceptive–common microRNAs and therapeutic strategies in liver cancer and melanoma. Cells, 9 (1):114.
16. Mourelatos Z, Dostie J, Paushkin S, et al (2002). miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs. Genes Dev, 16 (6):720-728.
17. Verma A, Singh V, Jaiswal PK, Mittal RD (2019). Anomalies in miRNAs machinery gene, GEMIN-4 variants suggest renal cell carcinoma risk: a small experimental study from North India. Indian J Clin Biochem, 34:45-51.
18. Lin J, Horikawa Y, Tamboli P, et al (2010). Genetic variations in microRNA-related genes are associated with survival and recurrence in patients with renal cell carcinoma. Carcinogenesis, 31 (10):1805-1812.
19. Liu J, Liu J, Wei M, et al (2012). Genetic variants in the microRNA machinery gene GEMIN4 are associated with risk of prostate cancer: a case-control study of the Chinese Han population. DNA Cell Biol, 31 (7):1296-1302.
20. Wu N, Zhang X, Tian J, et al (2017). Association of GEMIN4 gene polymorphism and the risk of cancer: a meta-analysis. Onco Targets Ther, 10:5263-5271.
21. Zhu W, Zhao J, He J, et al (2016). Genetic variants in the MicroRNA biosynthetic pathway Gemin3 and Gemin4 are associated with a risk of cancer: a meta-analysis. PeerJ, 4:e1724.
22. Sazer S, Dasso M (2000). The ran decathlon: multiple roles of Ran. J Cell Sci, 113 (Pt 7):1111-1118.
23. Lund E, Guttinger S, Calado A, et al (2004). Nuclear export of microRNA precursors. Science, 303 (5654):95-98.
24. Xia F, Lee CW, Altieri DC (2008). Tumor cell dependence on Ran-GTP–directed Mitosis. Cancer Res, 68 (6):1826-1833.
25. Barrès V, Ouellet V, Lafontaine J, et al (2010). An essential role for Ran GTPase in epithelial ovarian cancer cell survival. Mol Cancer, 9:272.
26. Abe H, Kamai T, Shirataki H, et al (2008). High expression of Ran GTPase is associated with local invasion and metastasis of human clear cell renal cell carcinoma. Int J Cancer, 122 (10):2391-2397.
27. Kurisetty V, Johnston P, Johnston N, et al (2008). RAN GTPase is an effector of the invasive/metastatic phenotype induced by osteopontin. Oncogene, 27 (57):7139-7149.
28. Li Y, Zhang F, Xing C (2020). A Systematic Review and Meta‐Analysis for the Association of Gene Polymorphisms in RAN with Cancer Risk. Dis Markers, 2020:9026707.
29. Gautam A (2022). DNA and RNA Isolation Techniques for Non-experts. ed. Springer.
30. Ye S, Dhillon S, Ke X, et al (2001). An efficient procedure for genotyping single nucleotide polymorphisms. Nucleic Acids Res, 29 (17):E88-8.
31. Bologna NG, Schapire AL, Palatnik JF (2013). Processing of plant microRNA precursors. Brief Funct Genomics, 12 (1):37-45.
32. Wang X, Li D, Sun L, et al (2020). Regulation of the small GTPase Ran by miR-802 modulates proliferation and metastasis in colorectal cancer cells. Br J Cancer, 122 (11):1695-1706.
33. Shao Y, Shen Y, Zhao L, et al (2020). Association of microRNA biosynthesis genes XPO5 and RAN polymorphisms with cancer susceptibility: Bayesian hierarchical meta-analysis. J Cancer, 11 (8):2181-2191.
34. Osuch-Wojcikiewicz E, Bruzgielewicz A, Niemczyk K, et al (2015). Association of polymorphic variants of miRNA processing genes with larynx cancer risk in a polish population. Biomed Res Int, 2015:298378.
35. Zhang C, Sun C, Zhao Y, et al (2022). Overview of MicroRNAs as diagnostic and prognostic biomarkers for high-incidence cancers in 2021. Int J Mol Sci, 23 (19):11389.
36. Zhao Y, Du Y, Zhao S, Guo Z (2015). Single-nucleotide polymorphisms of microRNA processing machinery genes and risk of colorectal cancer. Onco Targets Ther, 8:421-425.
37. Luan N, Mu Y, Mu J, et al (2021). Dicer1 promotes colon cancer cell invasion and migration through modulation of tRF-20-MEJB5Y13 expression under hypoxia. Front Genet, 12:638244.
| Files | ||
| Issue | Vol 53 No 12 (2024) | |
| Section | Original Article(s) | |
| Keywords | ||
| Colorectal cancer Single-nucleotide polymorphisms Genetics | ||
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How to Cite
1.
Mobaraki M, Asadzadeh Aghdaei H, Angaji SA, Alhosseini-Mojarad E, Arbabian S. Genetic Variation in MiRNA Processing Machinery Genes and Susceptibility to Colorectal Cancer in the Iranian Population. Iran J Public Health. 2024;53(12):2812-2822.
