Volume 13, Issue 2 (Vol.13 No.2 Jul 2024)                   rbmb.net 2024, 13(2): 281-300 | Back to browse issues page

XML Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Jahantab M B, Salehi M, Koushki M, Farrokhi Yekta R, Amiri-Dashatan N, Rezaei-Tavirani* M. Modelling of miRNA-mRNA Network to Identify Gene Signatures with Diagnostic and Prognostic Value in Gastric Cancer: Evidence from In-Silico and In-Vitro Studies. rbmb.net 2024; 13 (2) :281-300
URL: http://rbmb.net/article-1-1426-en.html
Proteomics Research Center, School of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran & Zanjan Metabolic Diseases Research Center, Health and Metabolic Diseases Research Institute, Zanjan University of Medical Sciences, Zanjan, Iran.
Abstract:   (87 Views)
Background: Gastric cancer (GC) is a prevalent malignancy with high recurrence. Advances in systems biology have identified molecular pathways and biomarkers. This study focuses on discovering gene and miRNA biomarkers for diagnosing and predicting survival in GC patients.

Methods: Three sets of genes (GSE19826, GSE81948, and GSE112369) and two sets of miRNA expression (GSE26595, GSE78775) were obtained from the Gene Expression Omnibus (GEO), and subsequently, differentially expressed genes (DEGs) and miRNAs (DEMs) were identified. Functional pathway enrichment, DEG-miR-TF-protein–protein interaction network, DEM-mRNA network, ROC curve, and survival analyses were performed. Finally, qRT-PCR was applied to validate our results.

Results: From the high-throughput profiling studies of GC, we investigated 10 candidate mRNA and 7 candidate miRNAs as potential biomarkers. Expression analysis of these hubs revealed that 5 miRNAs (including miR-141-3p, miR-204-5p, miR-338-3p, miR-609, and miR-369-5p) were significantly upregulated compared to the controls. The genes with the highest degree included 6 upregulated and 4 downregulated genes in tumor samples compared to controls. The expression of miR-141-3p, miR-204-5p, SESTD1, and ANTXR1 were verified in vitro from these hub DEMs and DEGs. The findings indicated a decrease in the expression of miR-141-3p and miR-204-5p and increased expression of SESTD1 and ANTXR1 in GC cell lines compared to the GES-1 cell line.

Conclusions: The current investigation successfully recognized a set of prospective miRNAs and genes that may serve as potential biomarkers for GC's early diagnosis and prognosis.
Full-Text [PDF 724 kb]   (34 Downloads)    
Type of Article: Original Article | Subject: Molecular Biology
Received: 2024/07/9 | Accepted: 2024/12/8 | Published: 2025/01/4

References
1. Morgan E, Arnold M, Camargo MC, Gini A, Kunzmann AT, Matsuda T, et al. The current and future incidence and mortality of gastric cancer in 185 countries, 2020-40: A population-based modelling study. EClinicalMedicine. 2022;47:101404. [DOI:10.1016/j.eclinm.2022.101404] [PMID] []
2. Nooh M, Hakemi-Vala M, Nowroozi J, Fatemi S-R, Dezfulian M. Prediction of blood miRNA-mRNA regulatory network in gastric cancer. Rep Biochem Mol Biol. 2021;10(2):243-256. [DOI:10.52547/rbmb.10.2.243] [PMID] []
3. Sousa JF, Ham AJ, Whitwell C, Nam KT, Lee HJ, Yang HK, et al. Proteomic profiling of paraffin-embedded samples identifies metaplasia-specific and early-stage gastric cancer biomarkers. Am J Pathol. 2012;181(5):1560-72. [DOI:10.1016/j.ajpath.2012.07.027] [PMID] []
4. Necula L, Matei L, Dragu D, Neagu AI, Mambet C, Nedeianu S, et al. Recent advances in gastric cancer early diagnosis. World J Gastroenterol. 2019 7;25(17):2029-2044. [DOI:10.3748/wjg.v25.i17.2029] [PMID] []
5. Mahmoudivar S, Zarredar H, Asadi M, Zafari V, Hashemzadeh S, Farzaneh R, Asvadi Kermani T. Serum miR-23 and miR-150 Profiles as Biomarkers for Predicting Recurrence following Surgical Intervention in Colorectal Cancer Patients. Rep Biochem Mol Biol. 2024;12(4):540-549. [DOI:10.61186/rbmb.12.4.540] [PMID] []
6. Jelski W, Mroczko B. Molecular and Circulating Biomarkers of Gastric Cancer. Int J Mol Sci. 2022;23(14):7588. [DOI:10.3390/ijms23147588] [PMID] []
7. Xiao B, Liu Z, Li BS, Tang B, Li W, Guo G, et al. Induction of microRNA-155 during Helicobacter pylori infection and its negative regulatory role in the inflammatory response. J Infect Dis. 2009;200(6):916-25. [DOI:10.1086/605443] [PMID]
8. Liu X, Ma R, Yi B, Riker AI, Xi Y. MicroRNAs are involved in the development and progression of gastric cancer. Acta Pharmacol Sin. 2021;42(7):1018-1026. [DOI:10.1038/s41401-020-00540-0] [PMID] []
9. Amiri-Dashatan N, Koushki M, Naghi-Zadeh M, Razzaghi MR, Mohaghegh Shalmani H. Prognostic value of microRNA-125a/b family in patients with gastric cancer: a meta-analysis. Gastroenterol Hepatol Bed Bench. 2021;14(Suppl1):S1-S9.
10. Amiri-Dashatan N, Koushki M, Jalilian A, Ahmadi NA, Rezaei-Tavirani M. Integrated Bioinformatics Analysis of mRNAs and miRNAs Identified Potential Biomarkers of Oral Squamous Cell Carcinoma. Asian Pac J Cancer Prev. 2020;21(6):1841-1848. [DOI:10.31557/APJCP.2020.21.6.1841] [PMID] []
11. Amiri-Dashatan N, Koushki M, Rezaei Tavirani M, Ahmadi NA. Protein-Protein Interaction Network Analysis of Salivary Proteomic Data in Oral Cancer Cases. Asian Pac J Cancer Prev. 2018;19(6):1639-1645.
12. Amiri-Dashatan N, Yekta Farrokhi R, Rostami Nejad M, Nikzamir A. Pathway and network analysis in primary open angle glaucoma. Arc Adv Biosci. 2014;5(3): 92-101.
13. Amiri-Dashatan N, Koushki M, Abbaszadeh HA, Rostami-Nejad M, Rezaei-Tavirani M. Proteomics Applications in Health: Biomarker and Drug Discovery and Food Industry. Iran J Pharm Res. 2018;17(4):1523-1536.
14. Amiri-Dashatan N, Yekta RF, Koushki M, Arefi Oskouie A, Esfahani H, Taheri S, Kazemian E. Metabolomic study of serum in patients with invasive ductal breast carcinoma with LC-MS/MS approach. Int J Biol Markers. 2022;37(4):349-359. [DOI:10.1177/03936155221123343] [PMID]
15. Yao Y, Ni Y, Zhang J, Wang H, Shao S. The role of Notch signalling in gastric carcinoma: molecular pathogenesis and novel therapeutic targets. Oncotarget. 2017;8(32):53839-53853. [DOI:10.18632/oncotarget.17809] [PMID] []
16. Martinez-Outschoorn UE, Lin Z, Whitaker-Menezes D, Howell A, Sotgia F, Lisanti MP. Ketone body utilization drives tumor growth and metastasis. Cell Cycle. 2012;11(21):3964-71. [DOI:10.4161/cc.22137] [PMID] []
17. Cui W, Luo W, Zhou X, Lu Y, Xu W, Zhong S, et al. Dysregulation of Ketone Body Metabolism Is Associated With Poor Prognosis for Clear Cell Renal Cell Carcinoma Patients. Front Oncol. 2019;9:1422. [DOI:10.3389/fonc.2019.01422] [PMID] []
18. Murakami S, Okubo K, Tsuji Y, Sakata H, Hamada S, Hirayama R. Serum interleukin-12 levels in patients with gastric cancer. Surg Today. 2004;34(12):1014-9. [DOI:10.1007/s00595-004-2860-z] [PMID]
19. Puneet, Kazmi HR, Kumari S, Tiwari S, Khanna A, Narayan G. Epigenetic Mechanisms and Events in Gastric Cancer-Emerging Novel Biomarkers. Pathol Oncol Res. 2018;24(4):757-770. [DOI:10.1007/s12253-018-0410-z] [PMID]
20. Michalak EM, Burr ML, Bannister AJ, Dawson MA. The roles of DNA, RNA and histone methylation in ageing and cancer. Nat Rev Mol Cell Biol. 2019;20(10):573-589. [DOI:10.1038/s41580-019-0143-1] [PMID]
21. Mitani Y, Oue N, Hamai Y, Aung PP, Matsumura S, Nakayama H, et al. Histone H3 acetylation is associated with reduced p21(WAF1/CIP1) expression by gastric carcinoma. J Pathol. 2005;205(1):65-73. [DOI:10.1002/path.1684] [PMID]
22. Xia L, Wang Z, Wu X, Zeng T, Luo W, Hu X, et al. Multiplatform discovery and regulatory function analysis of structural variations in non-small cell lung carcinoma. Cell Rep. 2021;36(10):109660. [DOI:10.1016/j.celrep.2021.109660] [PMID]
23. Gu W, Sun Y, Zheng X, Ma J, Hu XY, Gao T, Hu MJ. Identification of Gastric Cancer-Related Circular RNA through Microarray Analysis and Bioinformatics Analysis. Biomed Res Int. 2018;2018:2381680. [DOI:10.1155/2018/2381680] [PMID] []
24. Chaudhary A, Hilton MB, Seaman S, Haines DC, Stevenson S, Lemotte PK, et al. TEM8/ANTXR1 blockade inhibits pathological angiogenesis and potentiates tumoricidal responses against multiple cancer types. Cancer Cell. 2012;21(2):212-26. [DOI:10.1016/j.ccr.2012.01.004] [PMID] []
25. Cai C, Dang W, Liu S, Huang L, Li Y, Li G, et al. Anthrax toxin receptor 1/tumor endothelial marker 8 promotes gastric cancer progression through activation of the PI3K/AKT/mTOR signalling pathway. Cancer Sci. 2020;111(4):1132-1145. [DOI:10.1111/cas.14326] [PMID] []
26. Li L, Jiang X, Zhang Q, Dong X, Gao Y, He Y, et al. Neuropilin-1 is associated with clinicopathology of gastric cancer and contributes to cell proliferation and migration as multifunctional co-receptors. J Exp Clin Cancer Res. 2016;35:16. [DOI:10.1186/s13046-016-0291-5] [PMID] []
27. Cao H, Li Y, Huang L, Bai B, Xu Z. Clinicopathological Significance of Neuropilin 1 Expression in Gastric Cancer: A Meta-Analysis. Dis Markers. 2020;2020:4763492. [DOI:10.1155/2020/4763492] [PMID] []
28. Li Y, Zhao J, Chen R, Chen S, Xu Y, Cai W. Integration of clinical and transcriptomics reveals programming of the lipid metabolism in gastric cancer. BMC Cancer. 2022;22(1):955. [DOI:10.1186/s12885-022-10017-4] [PMID] []
29. Sivaganesh V, Sivaganesh V, Scanlon C, Iskander A, Maher S, Lê T, Peethambaran B. Protein Tyrosine Phosphatases: Mechanisms in Cancer. Int J Mol Sci. 2021;22(23):12865. [DOI:10.3390/ijms222312865] [PMID] []
30. Javdani H, Mollaei H, Karimi F, Mahmoudi S, Farahi A, Mirzaei-Parsa MJ, Shahabi A. Review article epithelial to mesenchymal transition associated microRNAs in breast cancer. Mol Biol Rep. 2022;49(10):9963-9973. [DOI:10.1007/s11033-022-07553-4] [PMID]
31. Ardila HJ, Sanabria-Salas MC, Meneses X, Rios R, Huertas-Salgado A, Serrano ML. Circulating miR-141-3p, miR-143-3p and miR-200c-3p are differentially expressed in colorectal cancer and advanced adenomas. Mol Clin Oncol. 2019;11(2):201-207. [DOI:10.3892/mco.2019.1876] [PMID] []
32. Xiao J, Zhang F, Liu W, Zang W. Construction of epithelial-mesenchymal transition related miRNAs signatures as prognostic biomarkers in gastric cancer patients. bioRxiv. 2022:2022.09. 02.506322. [DOI:10.1101/2022.09.02.506322]
33. Huang M, Wu L, Qin Y, Li Z, Luo S, Qin H, et al. Anti-proliferative role and prognostic implication of miR-141 in gastric cancer. Am J Transl Res. 2016;8(8):3549-57.
34. Zhang B, Yin Y, Hu Y, Zhang J, Bian Z, Song M, et al. MicroRNA-204-5p inhibits gastric cancer cell proliferation by downregulating USP47 and RAB22A. Med Oncol. 2015;32(1):331. [DOI:10.1007/s12032-014-0331-y] [PMID]
35. Liu X, Pu K, Wang Y, Chen Y, Zhou Y. Gastric cancer-associated microRNA expression signatures: integrated bioinformatics analysis, validation, and clinical significance. Ann Transl Med. 2021;9(9):797. [DOI:10.21037/atm-21-1631] [PMID] []
36. Liu S, Suo J, Wang C, Sun X, Wang D, He L, et al. Downregulation of tissue miR-338-3p predicts unfavorable prognosis of gastric cancer. Cancer Biomark. 2017;21(1):117-122. [DOI:10.3233/CBM-170339] [PMID]
37. Guo B, Liu L, Yao J, Ma R, Chang D, Li Z, et al. miR-338-3p suppresses gastric cancer progression through a PTEN-AKT axis by targeting P-REX2a. Mol Cancer Res. 2014;12(3):313-21. [DOI:10.1158/1541-7786.MCR-13-0507] [PMID]
38. Sun F, Yu M, Yu J, Liu Z, Zhou X, Liu Y, et al. miR-338-3p functions as a tumor suppressor in gastric cancer by targeting PTP1B. Cell Death Dis. 2018;9(5):522. [DOI:10.1038/s41419-018-0611-0] [PMID] []
39. Wang YN, Chen ZH, Chen WC. Novel circulating microRNAs expression profile in colon cancer: a pilot study. Eur J Med Res. 2017;22(1):51. https://doi.org/10.1186/s40001-020-00452-z https://doi.org/10.1186/s40001-014-0051-y [DOI:10.1186/s40001-017-0294-5]
40. Hu YJ, Zhang JY, Luo Q, Xu JR, Yan Y, Mu LM, et al. Nanostructured Dihydroartemisinin Plus Epirubicin Liposomes Enhance Treatment Efficacy of Breast Cancer by Inducing Autophagy and Apoptosis. Nanomaterials (Basel). 2018;8(10):804. [DOI:10.3390/nano8100804] [PMID] []
41. Wang Q, Wen YG, Li DP, Xia J, Zhou CZ, Yan DW, et al. Upregulated INHBA expression is associated with poor survival in gastric cancer. Med Oncol. 2012;29(1):77-83. [DOI:10.1007/s12032-010-9766-y] [PMID]
42. Canu V, Sacconi A, Lorenzon L, Biagioni F, Lo Sardo F, Diodoro MG, et al. MiR-204 down-regulation elicited perturbation of a gene target signature common to human cholangiocarcinoma and gastric cancer. Oncotarget. 2017;8(18):29540-29557. [DOI:10.18632/oncotarget.15290] [PMID] []
43. Nanki K, Toshimitsu K, Takano A, Fujii M, Shimokawa M, Ohta Y, et al. Divergent Routes toward Wnt and R-spondin Niche Independency during Human Gastric Carcinogenesis. Cell. 2018;174(4):856-869.e17. [DOI:10.1016/j.cell.2018.07.027] [PMID]
44. Lim JY, Yoon SO, Seol SY, Hong SW, Kim JW, Choi SH, et al. Overexpression of miR-196b and HOXA10 characterize a poor-prognosis gastric cancer subtype. World J Gastroenterol. 2013;19(41):7078-88. [DOI:10.3748/wjg.v19.i41.7078] [PMID] []
45. Yu B, Lv X, Su L, Li J, Yu Y, Gu Q, et al. MiR-148a Functions as a Tumor Suppressor by Targeting CCK-BR via Inactivating STAT3 and Akt in Human Gastric Cancer. PLoS One. 2016;11(8):e0158961. [DOI:10.1371/journal.pone.0158961] [PMID] []

Add your comments about this article : Your username or Email:
CAPTCHA

Send email to the article author


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

© 2015 All Rights Reserved | Reports of Biochemistry and Molecular Biology

Designed & Developed by : Yektaweb