Variant analysis of MiRNA regulatory genes in colorectal cancer

Yıl 2024, , 98 - 104, 15.01.2024

Özkan Bağcı , Ebru Marzioğlu-özdemir , Batuhan Şanlıtürk

https://doi.org/10.32322/jhsm.1403868

Öz

Aims: The aim of this study was to investigate the clinical significance of mutations in AGO2, DICER and DROSHA genes, which are involved in miRNA biogenesis, as well as TP53, KRAS, BRAF, PI3KCA and APC genes, which are important in the pathophysiology of CRC, and their association with metastasis in patients diagnosed with sporadic colorectal cancer
Methods: DNA isolation was performed by taking 10-micron sections from paraffin-embedded tissue samples of 12 patients diagnosed with CRC and Kapa NGS DNA extraction kit was used for sequence analysis. The purity and concentration of the DNA obtained was measured by Qubit fluoremeter, and NadPrep DNA Universal Library Preparation Kit was used for high quality library preparation. Bioinformatics analyses were performed on the Genomize Seq platform.
Results: In our study, metastasis was detected in 42% of 12 colorectal cancer patients. Mutations in at least two miRNA biogenesis genes were detected in 80% of metastatic patients. In addition, variants detected in miRNA biogenesis regulatory genes and oncogenic genes were summarized according to pathogenicity status according to the American College of Medical Genetics and Genomics (ACMG) classification.
Conclusion: Genes involved in miRNA biogenesis and mutations of clinically relevant genes in CRC have important implications on disease prognosis and response to therapy. Mutations in these genes may be associated with the development of metastases and mechanisms of resistance to treatment and may be potential genetic markers for the development of personalized treatment strategies.

Anahtar Kelimeler

Colorectal cancer, miRNA biogenesis, AGO2, DICER, DROSHA

Etik Beyan

Etik kurul onay belgesi ekte sunulmuştur.

Kaynakça

• Sager R. Expression genetics in cancer: shifting the focus from DNA to RNA. Proc Natl Acad Sci USA. 1997;94(3):952-955. doi:10.1073/pnas.94.3.952
• You JS, Jones PA. Cancer genetics and epigenetics: two sides of the same coin? Cancer Cell. 2012;22(1):9-20. doi:10.1016/j.ccr.2012.06.008
• Shen H, Laird PW. Interplay between the cancer genome and epigenome. Cell. 2013;153(1):38-55. doi:10.1016/j.cell.2013.03.008
• Ganju A, Khan S, Hafeez BB, et al. miRNA nanotherapeutics for cancer. Drug Discov Today. 2017;22(2):424-432. doi:10.1016/j.drudis.2016.10.014
• Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 2010;11(9):597-610. doi:10.1038/nrg2843
• Finnegan EF, Pasquinelli AE. MicroRNA biogenesis: regulating the regulators. Crit Rev Biochem Mol Biol. 2013;48(1):51-68. doi:10.3109/10409238.2012.738643
• Wu K, He J, Pu W, Peng Y. The role of exportin-5 in microRNA biogenesis and cancer. Genomics Proteomics Bioinformatics. 2018;16(2):120-126. doi:10.1016/j.gpb.2017.09.004
• Shomron N, Levy C. MicroRNA-biogenesis and pre-mRNA splicing crosstalk. J Biomed Biotechnol. 2009;2009:594678. doi:10.1155/2009/594678
• Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215-233. doi:10.1016/j.cell.2009.01.002
• Di Leva G, Garofalo M, Croce CM. MicroRNAs in cancer. Annu Rev Pathol. 2014;9(1):287-314. doi:10.1146/annurev-pathol-012 513-104715
• Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017;66(4):683-691. doi:10.1136/gutjnl-2015-310912
• Mármol I, Sánchez-de-Diego C, Pradilla Dieste A, Cerrada E, Rodriguez Yoldi MJ. Colorectal carcinoma: a general overview and future perspectives in colorectal cancer. Int J Mol Sci. 2017;18(1):197 doi:10.3390/ijms18010197
• Fleming M, Ravula S, Tatishchev SF, Wang HL. Colorectal carcinoma: pathologic aspects. J Gastrointest Oncol. 2012;3(3):153-173. doi:10.3978/j.issn.2078-6891.2012.030
• Tate JG, Bamford S, Jubb HC, et al. COSMIC: the catalogue of somatic mutations in cancer. Nucleic Acids Res. 2018;47(D1):D941-D947. doi:10.1093/nar/gky1015
• Zhu G, Pei L, Xia H, Tang Q, Bi F. Role of oncogenic KRAS in the prognosis, diagnosis and treatment of colorectal cancer. Mol Cancer. 2021;20(1):143. doi:10.1186/s12943-021-01441-4
• Gutierrez A, Demond H, Brebi P, Ili CG. Novel methylation biomarkers for colorectal cancer prognosis. Biomolecules. 2021;11(11):1722. doi:10.3390/biom11111722
• Jung G, Hernández-Illán E, Moreira L, Balaguer F, Goel A. Epigenetics of colorectal cancer: biomarker and therapeutic potential. Nat Rev Gastroenterol Hepatol. 2020;17(2):111-130. doi:10.1038/s41575-019-0230-y
• Tanoglu A, Balta AZ, Berber U, et al. MicroRNA expression profile in patients with stage II colorectal cancer: a Turkish referral center study. Asian Pac J Cancer Prev. 2015;16(5):1851-1855. doi:10.7314/apjcp.2015.16.5.1851
• Muhammad S, Kaur K, Huang R, et al. MicroRNAs in colorectal cancer: role in metastasis and clinical perspectives. World J Gastroenterol. 2014;20(45):17011-17019. doi:10.3748/wjg.v20.i45.17011
• Jenike AE, Halushka MK. miR-21: a non-specific biomarker of all maladies. Biomark Res. 2021;9(1):18. doi:10.1186/s40364-021-00272-1
• He L, He X, Lim LP, et al. A microRNA component of the p53 tumour suppressor network. Nature. 2007;447(7148):1130-1134. doi:10.1038/nature05939
• Esquela-Kerscher A, Slack FJ. Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 2006;6(4):259-269. doi:10.1038/nrc1840
• Bandara KV, Michael MZ, Gleadle JM. MicroRNA biogenesis in hypoxia. Microrna. 2017;6(2):80-96. doi:10.2174/2211536606666170313114821
• Ahluwalia P, Kolhe R, Gahlay GK. The clinical relevance of gene expression based prognostic signatures in colorectal cancer. Biochim Biophys Acta Rev Cancer. 2021;1875(2):188513. doi:10.1016/j.bbcan.2021.188513
• Sun L, Fang Y, Wang X, et al. miR-302a inhibits metastasis and cetuximab resistance in colorectal cancer by targeting NFIB and CD44. Theranostics. 2019;9(26):8409-8425. doi:10.7150/thno.36605
• Su R, Wu X, Tao L, Wang C. The role of epigenetic modifications in colorectal cancer metastasis. Clin Exp Metastasis. 2022;39(4):521-539. doi:10.1007/s10585-022-10163-w
• Van Cutsem E, Cervantes A, Nordlinger B, Arnold D. Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(Suppl 3):iii1-iii9. doi:10.1093/annonc/mdu260
• Hong Y, Liang H, Uzair ur R, et al. miR-96 promotes cell proliferation, migration and invasion by targeting PTPN9 in breast cancer. Scientif Rep. 2016;6(1):37421. doi:10.1038/srep37421
• Yu S, Lu Z, Liu C, et al. miRNA-96 suppresses KRAS and functions as a tumor suppressor gene in pancreatic cancer. Cancer Res. 2010;70(14):6015-6025. doi:10.1158/0008-5472.Can-09-4531
• Chen X, Guo X, Zhang H, et al. Role of miR-143 targeting KRAS in colorectal tumorigenesis. Oncogene. 2009;28(10):1385-1392. doi:10.1038/onc.2008.474
• Lin S, Gregory RI. MicroRNA biogenesis pathways in cancer. Nat Rev Cancer. 2015;15(6):321-333. doi:10.1038/nrc3932
• Szczyrek M, Grenda A, Kuźnar-Kamińska B, et al. Methylation of DROSHA and DICER as a biomarker for the detection of lung cancer. Cancers. 2021;13(23):6139. doi:10.3390/cancers13236139
• Sung H, Jeon S, Lee KM, et al. Common genetic polymorphisms of microRNA biogenesis pathway genes and breast cancer survival. BMC Cancer. 2012;12:195. doi:10.1186/1471-2407-12-195
• Galka-Marciniak P, Urbanek-Trzeciak MO, Nawrocka PM, et al. Somatic mutations in miRNA genes in lung cancer-potential functional consequences of non-coding sequence variants. Cancers. 2019;11(6):793. doi:10.3390/cancers11060793
• Chen HY, Wang ML, Laurent B, et al. Musashi-1 promotes stress-induced tumor progression through recruitment of AGO2. Theranostics. 2020;10(1):201-217. doi:10.7150/thno.35895
• Ke HL, Chen M, Ye Y, et al. Genetic variations in micro-RNA biogenesis genes and clinical outcomes in non-muscle-invasive bladder cancer. Carcinogenesis. 2013;34(5):1006-1011. doi:10.1093/carcin/bgt006
• Rakheja D, Chen KS, Liu Y, et al. Somatic mutations in DROSHA and DICER1 impair microRNA biogenesis through distinct mechanisms in Wilms tumours. Nat Commun. 2014;2:4802. doi:10.1038/ncomms5802
• Boni V, Zarate R, Villa JC, et al. Role of primary miRNA polymorphic variants in metastatic colon cancer patients treated with 5-fluorouracil and irinotecan. Pharmacogenomics J. 2011;11(6):429-436. doi:10.1038/tpj.2010.58
• Testa U, Pelosi E, Castelli G. Colorectal cancer: genetic abnormalities, tumor progression, tumor heterogeneity, clonal evolution and tumor-initiating cells. Med Sci. 2018;6(2):31. doi: 10.3390/medsci6020031