Molecular characterization of colorectal cancer: Insights from miRNA, mRNA, and protein analysis
Recent research highlights the significant roles of microRNAs (miRNAs) in various diseases, particularly cancer, where they serve as diagnostic and prognostic markers. This study focuses on colorectal cancer (CRC) by examining the expression of six specific miRNAs, miR-20a, miR-21, miR-29a, miR-31, miR-92a, and miR-224, in 81 tumor samples compared to matched normal tissues. We assessed the expression levels of six target genes, SMAD4, PTEN, TGFBRII, BCL2, KLF4, and RASA1, using reverse transcription quantitative polymerase chain reaction and immunohistochemistry. Our results indicated a significant upregulation of miR-20a, miR-21, miR-29a, and miR-31 in tumor samples, alongside a decrease in TGFBRII mRNA expression. Correlation analyses demonstrated that high levels of miR-20a were inversely related to both mRNA and protein levels of PTEN. Elevated expressions of miR-21 and miR-224 were associated with lower mRNA and protein levels of TGFBRII. Furthermore, increased levels of miR-29a and miR-31 showed an inverse relationship with mRNA and protein levels of RASA1. These findings suggest a strong link between upregulated miRNAs and downregulated target genes, indicating their significant roles in CRC carcinogenesis. Notably, the upregulation of miR-20a, miR-21, miR-29a, and miR-31 may serve as effective biomarkers for differentiating CRC from normal mucosa, potentially enhancing screening strategies in the general population.
- Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: Incidence, mortality, survival, and risk factors. Prz Gastroenterol. 2019;14(2):89-103. doi: 10.5114/pg.2018.81072
- Olivier T, Fernandez E, Labidi-Galy I, et al. Redefining cancer of unknown primary: Is precision medicine really shifting the paradigm? Cancer Treat Rev. 2021;97:102204. doi: 10.1016/j.ctrv.2021.102204
- Ždralević M, Raonić J, Popovic N, et al. The role of miRNA in colorectal cancer diagnosis: A pilot study. Oncol Lett. 2023;25(6):267. doi: 10.3892/ol.2023.13853
- Kim SM, Choi HS, Byun JS. Overall 5-year survival rate and prognostic factors in patients with stage IB and IIA cervical cancer treated by radical hysterectomy and pelvic lymph node dissection. Int J Gynecol Cancer. 2000;10(4):305-312. doi: 10.1046/j.1525-1438.2000.010004305.x
- Coleman D, Kuwada S. miRNA as a Biomarker for the early detection of colorectal cancer. Genes (Basel). 2024;15(3):338. doi: 10.3390/genes15030338
- Kral J, Kojecky V, Stepan M, et al. The experience with colorectal cancer screening in the Czech Republic: The detection at earlier stages and improved clinical outcomes. Public Health. 2020;185:153-158. doi: 10.1016/j.puhe.2020.05.021
- Ji Y, Jialin G, Hongqun Z, Houxi X. Identification and validation of Key miRNAs for colon cancer based on miRNA-gene integration analysis. Int J Gen Med. 2023;(16):5703-5718. doi: 10.2147/IJGM.S440340
- Sadeghi S, Lotfi M, Soltani N, et al. Recent advances on high-efficiency of microRNAs in different types of lung cancer: A comprehensive review. Cancer Cell Int. 2023;23(1):284. doi: 10.1186/s12935-023-03133-z
- Sado AI, Batool W, Ahmed A, et al. Role of microRNA in colorectal carcinoma (CRC): A narrative review. Ann Med Surg (Lond). 2023;86(1):308-318. doi: 10.1097/MS9.0000000000001494
- Koncina E, Haan S, Rauh S, Letellier E. Prognostic and predictive molecular biomarkers for colorectal cancer: Updates and challenges. Cancers (Basel). 2020;12(2):319. doi: 10.3390/cancers12020319
- Cheng D, Zhao S, Tang H, et al. MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4. Oncotarget. 2016;7(29):45199-45213. doi: 10.18632/oncotarget.9900
- Sun LH, Tian D, Yang ZC, Li JL. Exosomal miR-21 promotes proliferation, invasion and therapy resistance of colon adenocarcinoma cells through its target PDCD4. Sci Rep. 2020;10(1):8271. doi: 10.1038/s41598-020-65207-6
- Wang J, Chen X, Xie C, et al. MicroRNA miR-29a inhibits colon cancer progression by downregulating B7-H3 expression: Potential molecular targets for colon cancer therapy. Mol Biotechnol. 2021;63(9):849-861 doi: 10.1007/s12033-021-00348-1
- Kent OA, Mendell JT, Rottapel R. Transcriptional regulation of miR-31 by Oncogenic KRAS mediates metastatic phenotypes by repressing RASA1. Mol Cancer Res. 2016;14(3):267-277. doi: 10.1158/1541-7786.MCR-15-0456
- Li Y, Li K, Lou X, et al. HNRNPA2B1-mediated microRNA- 92a upregulation and section acts as a promising noninvasive diagnostic biomarker in colorectal cancer. Cancers (Basel). 2023;15(4):1367. doi: 10.3390/cancers15051367
- Li T, Lai Q, Wang S, et al. MicroRNA-224 sustains Wnt/β- catenin signaling and promotes aggressive phenotype of colorectal cancer. J Exp Clin Cancer Res. 2016;35:21. doi: 10.1186/s13046-016-0287-1. Erratum in: J Exp Clin Cancer Res. 2021;40(1):143. doi: 10.1186/s13046-021-01945-3
- Sun D, Yu F, Ma Y, et al. MicroRNA-31 activates the RAS pathway and functions as an oncogenic MicroRNA in human colorectal cancer by repressing RAS p21 GTPase activating protein 1 (RASA1). J Biol Chem. 2013;288(13):9508-9518. doi: 10.1074/jbc.M112.367763
- Zhang G, Zhou H, Xiao H, Liu Z, Tian H, Zhou T. MicroRNA-92a functions as an oncogene in colorectal cancer by targeting PTEN. Dig Dis Sci. 2014;59(1):98-107. doi: 10.1007/s10620-013-2858-8
- Mo WY, Cao SQ. MiR-29a-3p: A potential biomarker and therapeutic target in colorectal cancer. Clin Transl Oncol. 2023;25(3):563-577. doi: 10.1007/s12094-022-02978-6
- Sokolova V, Fiorino A, Zoni E, et al. The effects of miR- 20a on p21: Two mechanisms blocking growth arrest in TGF-β-responsive colon carcinoma. J Cell Physiol. 2015;230(12):3105-3114. doi: 10.1002/jcp.25051
- Michas A, Michas V, Anagnostou E. The clinical significance of MicroRNAs in colorectal cancer signaling pathways: A review. Glob Med Genet. 2023;10(4):315-323. doi: 10.1055/s-0043-1777094
- Chretien AS, Harlé A, Meyer-Lefebvre M, et al. Optimization of routine KRAS mutation PCR-based testing procedure for rational individualized first-line-targeted therapy selection in metastatic colorectal cancer. Cancer Med. 2013;2(1):11-20. doi: 10.1002/cam4.47
- Díaz R, Silva J, García JM, et al. Deregulated expression of miR-106a predicts survival in human colon cancer patients. Genes Chromosomes Cancer. 2008;47(9):794-802. doi: 10.1002/gcc.20580
- Ng EK, Chong WW, Jin H, et al. Differential expression of microRNAs in plasma of patients with colorectal cancer: A potential marker for colorectal cancer screening. Gut. 2009;58(10):1375-1381. doi: 10.1136/gut.2008.167817
- Abd El-Rehim DM, Ball G, Pinder SE, et al. High-throughput protein expression analysis using tissue microarray technology of a large well-characterised series identifies biologically distinct classes of breast cancer confirming recent cDNA expression analyses. Int J Cancer. 2005;116(3):340-350. doi: 10.1002/ijc.21004
- Pandey S, Jain A, Vagha S. Insights into colorectal carcinoma: A comprehensive review of MicroRNA expression patterns. Cureus. 2024;16(3):e56739. doi: 10.7759/cureus.56739
- 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
- Al-Nakhle HH. Unraveling the multifaceted role of the miR-17-92 cluster in colorectal cancer: From mechanisms to biomarker potential. Curr Issues Mol Biol. 2024;46(3):1832-1850. doi: 10.3390/cimb46030120
- Santos DAR, Gaiteiro C, Santos M, Santos L, Dinis-Ribeiro M, Lima L. MicroRNA biomarkers as promising tools for early colorectal cancer screening-a comprehensive review. Int J Mol Sci. 2023;24(13):11023. doi: 10.3390/ijms241311023
- Fellizar A, Refuerzo V, Ramos JD, Albano PM. Expression of specific microRNAs in tissue and plasma in colorectal cancer. J Pathol Transl Med. 2023;57(3):147-157. doi: 10.4132/jptm.2022.02.19
- Schepeler T, Reinert JT, Ostenfeld MS, et al. Diagnostic and prognostic microRNAs in stage II colon cancer. Cancer Res. 2008;68(15):6416-6424. doi: 10.1158/0008-5472.CAN-07-6110
- Zhou T, Zhang G, Liu Z, Xia S, Tian H. Overexpression of miR-92a correlates with tumor metastasis and poor prognosis in patients with colorectal cancer. Int J Colorectal Dis. 2013;28(1):19-24. doi: 10.1007/s00384-012-1528-1
- Liu C, Yu C, Song G, et al. Comprehensive analysis of miRNA-mRNA regulatory pairs associated with colorectal cancer and the role in tumor immunity. BMC Genomics. 2023;24(1):724 doi: 10.1186/s12864-023-09635-4
- Prakash S, Alisha G. MicroRNAs: Potential biomarkers for diagnosis and prognosis of different cancers. Transl Cancer Res. 2020;9(9):5798-5818. doi: 10.21037/tcr-20-1294
- Ramesh P, Medema JP. BCL-2 family deregulation in colorectal cancer: Potential for BH3 mimetics in therapy. Apoptosis. 2020;25(5-6):305-320. doi: 10.1007/s10495-020-01601-9
- Yu T, Ma P, Wu D, Shu Y, Gao W. Functions and mechanisms of microRNA-31 in human cancers. Biomed Pharmacother. 2018;108:1162-1169. doi: 10.1016/j.biopha.2018.09.132
- Ahadi A. The significance of microRNA deregulation in colorectal cancer development and the clinical uses as a diagnostic and prognostic biomarker and therapeutic agent. Noncoding RNA Res. 2020;5(3):125-134. doi: 10.1016/j.ncrna.2020.08.003
- Sasso CV, Lhamyani S, Hevilla F, et al. Modulation of miR- 29a and miR-29b Expression and their target genes related to inflammation and renal fibrosis by an oral nutritional supplement with probiotics in malnourished hemodialysis patients. Int J Mol Sci. 2024;25:1132. doi: 10.3390/ijms25021132