Categorized Serum miRNAs as Potential Biomarkers for Predicting the Progression and Prognosis of Colorectal Cancer

Oğuz , Meral Merve; Khademi Siahestalkhi, Ehteram; Yaren , Arzu; Demiray , Aydin; Gökçen Demiray , Atike

doi:10.61186/ijbc.16.2.7

Volume 16, Issue 2 (June 2024 2024) Iranian Journal of Blood and Cancer 2024, 16(2): 7-14 | Back to browse issues page

‎ 10.61186/ijbc.16.2.7

Mendeley

Zotero

RefWorks

Oğuz M M, Khademi Siahestalkhi E, Yaren A, Demiray A, Gökçen Demiray A. Categorized Serum miRNAs as Potential Biomarkers for Predicting the Progression and Prognosis of Colorectal Cancer. Iranian Journal of Blood and Cancer 2024; 16 (2) :7-14
URL: http://ijbc.ir/article-1-1556-en.html

Categorized Serum miRNAs as Potential Biomarkers for Predicting the Progression and Prognosis of Colorectal Cancer

Meral Merve Oğuz¹

, Ehteram Khademi Siahestalkhi ^*²

, Arzu Yaren¹

, Aydin Demiray³

, Atike Gökçen Demiray¹

1- Department of Internal Medicine, Pamukkale University, Denizli, Turkey/ The Affiliated Hospital of Pamukkale University.
2- Department of Medical Genetics, Faculty of Medicine, Pamukkale University, Denizli, Turkey. , e.khademi18@gmail.com
3- Department of Medical Genetics, Faculty of Medicine, Pamukkale University, Denizli, Turkey.

Abstract: (775 Views)

Background: Colorectal cancer (CRC), a common and aggressive gastrointestinal cancer, presents significant challenges in diagnosis and prognosis prediction despite available detection and treatment options. Many studies emphasized the crucial link between abnormal microRNA regulation and their potential role in cancer development and progression. These miRNAs are recognized as important non-invasive biomarkers for prognosis and overall survival prediction in various cancers, including CRC.
Materials and Methods: In this study, we compared the expression patterns of eight miRNAs in the serum of 36 CRC patients with those of 37 healthy controls. The matching criteria included clinicodemographic factors and CRC susceptibility, and the analysis was performed using quantitative real-time PCR (qRT-PCR).
Results: The serum miRNA levels of these eight miRNAs (miR-19a, miR-92a, miR-103, miR-106a, miR-107a, miR-150, miR-221, and miR-720) in the study groups are significantly higher compared to the control group. This analysis revealed eight specific miRNAs with varying expression levels in CRC patients. Furthermore, bioinformatic analysis using data collection and analytical tools has shown that these miRNAs may be associated with important aspects of colorectal cancer development and progression through the PI3K/AKT/PTEN, WNT/CATENIN, and EMT signaling pathways.Conclusion: Our analysis has identified a group of 8 overexpressed miRNAs (miR-19a, miR-92a, miR-103, miR-106a, miR-107a, miR-150, miR-221, and miR-720.) in serum samples of CRC patients. : Although further validation in larger and more diverse groups is necessary, these findings support a potential mechanism of action for these miRNAs in CRC and their association with essential signaling pathways, including PI3K/AKT/PTEN, WNT/CATENIN, and EMT.

Keywords: Colorectal cancer (CRC), microRNAs (miRNAs), Biomarkers, Prognosis, PI3K/AKT/PTEN, WNT/CATENIN, EMT

Full-Text [PDF 656 kb] (240 Downloads)

: Original Article | Subject: Adults Hematology & Oncology
Received: 2024/05/11 | Accepted: 2024/06/15 | Published: 2024/06/30

References

1. Hoseini SH, Enayati P, Nazari M, Babakhanzadeh E, Rastgoo M, Sohrabi NB. Biomarker Profile of Colorectal Cancer: Current Findings and Future Perspective. J Gastrointest Cancer. 2024 Jan 2; [DOI:10.1007/s12029-023-00990-9]

2. Keum N, Giovannucci E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol. 2019 Dec;16(12):713-32. [DOI:10.1038/s41575-019-0189-8]

3. Zlobec I, Lugli A. Prognostic and predictive factors in colorectal cancer. Postgrad Med J. 2008 Aug;84(994):403-11. [DOI:10.1136/jcp.2007.054858]

4. Schreuders EH, Ruco A, Rabeneck L, Schoen RE, Sung JJ, Young GP, et al. Colorectal cancer screening: a global overview of existing programs. Gut. 2015 Oct;64(10):1637-49. [DOI:10.1136/gutjnl-2014-309086]

5. Allison JE, Tekawa IS, Ransom LJ, Adrain AL. A comparison of fecal occult blood tests for colorectal-cancer screening. N Engl J Med. 1996;334(3):155-9. [DOI:10.1056/NEJM199601183340304]

6. Koh JL, Yan TD, Glenn D, Morris DL. Evaluation of preoperative computed tomography in estimating peritoneal cancer index in colorectal peritoneal carcinomatosis. Ann Surg Oncol. 2009 Feb;16(2):327-33. [DOI:10.1245/s10434-008-0234-2]

7. Motalleb G, Sancholi S, Yegane Moghadam A, Talaee R. P53 gene expression evaluation in patients with esophageal cancer using reverse transcriptase real-time polymerase chain reaction. Pajoohandeh J [Internet]. 2015 Aug 10 [cited 2024 Jun 4];20(3):154-62. Available from: http://pajoohande.sbmu.ac.ir/article-1-2023-en.html

8. Stein, L. C D. Reactome: a database of reactions, pathways and biological processes. Nucleic Acids Research, [Internet]. 2010. Available from: https://reactome.org/

9. KEGG: Kyoto Encyclopedia of genes and genomes - PubMed [Internet]. [cited 2024 May 30]. Available from: https://pubmed.ncbi.nlm.nih.gov/10592173/

10. miRBase [Internet]. [cited 2024 May 30]. Available from: https://www.mirbase.org/

11. miRTarBase: the experimentally validated microRNA-target interactions database [Internet]. [cited 2024 May 30]. Available from: https://mirtarbase.cuhk.edu.cn/~miRTarBase/miRTarBase_2022/php/index.php

12. TargetScanHuman 8.0 [Internet]. [cited 2024 May 30]. Available from: https://www.targetscan.org/vert_80/

13. Enrichr [Internet]. [cited 2024 May 30]. Available from: https://maayanlab.cloud/Enrichr/

14. DAVID Functional Annotation Bioinformatics Microarray Analysis [Internet]. [cited 2024 May 30]. Available from: https://david.ncifcrf.gov/

15. Sherman BT, Hao M, Qiu J, Jiao X, Baseler MW, Lane HC, et al. DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res. 2022 Jul 5;50(W1): W216-21. [DOI:10.1093/nar/gkac194]

16. Cytoscape: An Open Source Platform for Complex Network Analysis and Visualization [Internet]. [cited 2024 May 30]. Available from: https://cytoscape.org/

17. Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res [Internet]. 2019 Jan 8 [cited 2024 May 30];47(D1):D607-13. Available from: [DOI:10.1093/nar/gky1131]

18. Zhang GJ, Li LF, Yang GD, Xia SS, Wang R, Leng ZW, et al. MiR-92a promotes stem cell-like properties by activating Wnt/β-catenin signaling in colorectal cancer. Oncotarget. 2017 Nov 24;8(60):101760-70. [DOI:10.18632/oncotarget.21667]

19. Liu Y, Liu R, Yang F, Cheng R, Chen X, Cui S, et al. miR-19a promotes colorectal cancer proliferation and migration by targeting TIA1. Mol Cancer. 2017 Mar 4;16(1):53. [DOI:10.1186/s12943-017-0625-8]

20. Dou L, Meng X, Sui X, Wang S, Shen T, Huang X, et al. MiR-19a regulates PTEN expression to mediate glycogen synthesis in hepatocytes. Sci Rep. 2015;5:11602. [DOI:10.1038/srep11602]

21. Colakoglu T, Yildirim S, Kayaselcuk F, Nursal TZ, Ezer A, Noyan T, et al. Clinicopathological significance of PTEN loss and the phosphoinositide 3-kinase/Akt pathway in sporadic colorectal neoplasms: is PTEN loss predictor of local recurrence? Am J Surg. 2008 Jun;195(6):719-25. [DOI:10.1016/j.amjsurg.2007.05.061]

22. Peng Y, Huang D, Qing X, Tang L, Shao Z. Investigation of MiR-92a as a Prognostic Indicator in Cancer Patients: a Meta-Analysis. J Cancer. 2019;10(18):4430-41. [DOI:10.7150/jca.30313]

23. Zheng YB, Xiao K, Xiao GC, Tong SL, Ding Y, Wang QS, et al. MicroRNA-103 promotes tumor growth and metastasis in colorectal cancer by directly targeting LATS2. Oncol Lett. 2016 Sep;12(3):2194-200. [DOI:10.3892/ol.2016.4814]

24. Geng L, Sun B, Gao B, Wang Z, Quan C, Wei F, et al. MicroRNA-103 promotes colorectal cancer by targeting tumor suppressors DICER and PTEN. Int J Mol Sci. 2014 May 13;15(5):8458-72. [DOI:10.3390/ijms15058458]

25. Nonaka R, Miyake Y, Hata T, Kagawa Y, Kato T, Osawa H, et al. Circulating miR-103 and miR-720 as novel serum biomarkers for patients with colorectal cancer. Int J Oncol. 2015 Sep;47(3):1097-102. [DOI:10.3892/ijo.2015.3064]

26. Liu J, Ke F, Chen T, Zhou Q, Weng L, Tan J, et al. MicroRNAs that regulate PTEN as potential biomarkers in colorectal cancer: a systematic review. J Cancer Res Clin Oncol. 2020;146(4):809-20. [DOI:10.1007/s00432-020-03172-3]

27. Hao H, Xia G, Wang C, Zhong F, Liu L, Zhang D. miR-106a suppresses tumor cell death in colorectal cancer through targeting ATG7. Med Mol Morphol. 2017;50(2):76-85. [DOI:10.1007/s00795-016-0150-7]

28. Yu FB, Sheng J, Yu JM, Liu JH, Qin XX, Mou B. MiR-19a-3p regulates the Forkhead box F2-mediated Wnt/β-catenin signaling pathway and affects the biological functions of colorectal cancer cells. World J Gastroenterol. 2020 Feb 14;26(6):627-44. [DOI:10.3748/wjg.v26.i6.627]

29. Chen HY, Lin YM, Chung HC, Lang YD, Lin CJ, Huang J, et al. miR-103/107 Promote Metastasis of Colorectal Cancer by Targeting the Metastasis Suppressors DAPK and KLF4. Cancer Res. 2012;72(14):3631-41. [DOI:10.1158/0008-5472.CAN-12-0667]

30. Chen HY, Lang YD, Lin HN, Liu YR, Liao CC, Nana AW, et al. miR-103/107 prolong Wnt/β-catenin signaling and colorectal cancer stemness by targeting Axin2. Sci Rep. 2019 Jul 4;9(1):9687. [DOI:10.1038/s41598-019-41053-z]

31. Guo YH, Wang LQ, Li B, Xu H, Yang JH, Zheng LS, et al. The Wnt/β-catenin pathway transactivates microRNA-150 and promotes EMT of colorectal cancer cells by suppressing CREB signaling. Oncotarget. 2016 Jul 5;7(27):42513-26. [DOI:10.18632/oncotarget.9893]

32. Zhao F, Yang Z, Gu X, Feng L, Xu M, Zhang X. miR-92b-3p Regulates Cell Cycle and Apoptosis by Targeting CDKN1C, Thereby Affecting the Sensitivity of Colorectal Cancer Cells to Chemotherapeutic Drugs. Cancers. 2021;13(13):3323. [DOI:10.3390/cancers13133323]

33. Hong Z, Feng Z, Sai Z, Tao S. PER3, a novel target of miR-103, plays a suppressive role in colorectal cancer in vitro. BMB Rep. 2014 Sep;47(9):500-5. [DOI:10.5483/BMBRep.2014.47.9.212]

34. Debnath P, Huirem RS, Dutta P, Palchaudhuri S. Epithelial-mesenchymal transition and its transcription factors. Biosci Rep. 2022 Jan 28;42(1):BSR20211754. [DOI:10.1042/BSR20211754]

35. Li C, Du X, Xia S, Chen L. MicroRNA-150 inhibits the proliferation and metastasis potential of colorectal cancer cells by targeting iASPP. Oncol Rep. 2018; [DOI:10.3892/or.2018.6406]

36. Ameri A, Ahmed HM, Pecho RDC, Arabnozari H, Sarabadani H, Esbati R, et al. Diverse activity of miR-150 in Tumor development: shedding light on the potential mechanisms. Cancer Cell Int. 2023 Nov 3;23(1):261. [DOI:10.1186/s12935-023-03105-3]

37. Wang X, Kuang Y, Shen X, Zhou H, Chen Y, Han Y, et al. Evaluation of miR-720 prognostic significance in patients with colorectal cancer. Tumor Biol. 2015 Feb 1;36(2):719-27. [DOI:10.1007/s13277-014-2697-z]

Send email to the article author

Rights and permissions
	This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Designed & Developed by : Yektaweb