Expression of microRNAs in gastric cancerous tissues and their association with <em>Helicobacter pylori</em> and Epstein‑Barr virus infections

Rihane,Fatima Ezzahra; Erguibi,Driss; Abumsimir,Berjas; Charoute,Hicham; Chehab,Farid; Ennaji,Moulay Mustapha

doi:10.3892/wasj.2022.171

September-October 2022 Volume 4 Issue 5

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

September-October 2022 Volume 4 Issue 5

Full Size Image

Article Open Access

Expression of microRNAs in gastric cancerous tissues and their association with Helicobacter pylori and Epstein‑Barr virus infections

Authors:
- Fatima Ezzahra Rihane
- Driss Erguibi
- Berjas Abumsimir
- Hicham Charoute
- Farid Chehab
- Moulay Mustapha Ennaji
View Affiliations / Copyright

Affiliations: Laboratory of Genetic and Molecular Pathology, Faculty of Medicine and Pharmacy of Casablanca, University Hassan II of Casablanca, Casablanca 20250, Morocco, Service of Digestive Cancers Surgery and Liver Transplant, Department of Surgery, Ibn Rochd University Hospital Center, Faculty of Medicine and Pharmacy of Casablanca, University Hassan II of Casablanca, Casablanca 20250, Morocco, Pharmacological and Diagnostic Research Centre (PDRC), Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al‑Ahliyya Amman University (AAU), Amman 19328, Jordan, Research Unit of Epidemiology, Biostatistics and Bioinformatics, Pasteur Institute of Morocco, Casablanca 20360, Morocco, Laboratory of Virology, Microbiology, Quality, Biotechnologies/Ecotoxicology and Biodiversity, Faculty of Sciences and Technologies Mohammedia, University Hassan II of Casablanca, Mohammedia 20650, Morocco

Copyright: © Rihane et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 36
|
Published online on: September 13, 2022

https://doi.org/10.3892/wasj.2022.171
Expand metrics +

Abstract

Gastric cancer (GC) is a serious public health concern, being one of the most frequent types of cancer worldwide, and the most lethal of all gastrointestinal cancers. Among the numerous causes of the occurrence and progression of GC, are infections of the gastric epithelium by microbial agents, such as Epstein‑Barr virus and/or Helicobacter pylori (H. pylori). Recent findings have shed new light on the involvement of a class of non‑coding RNAs, known as microRNAs (miRNAs/miRs) that are differentially expressed in GC tissues. Among these miRNAs, miR‑21, miR‑223 and miR‑19, appear to play a crucial role in tumorigenesis. The present study aimed to investigate the differential expression of miR‑21, miR‑223 and miR‑19 in GC tissues and their association with Epstein‑Barr virus and H. pylori infections. The expression levels of miR‑21, miR‑223 and miR‑19 in 70 samples of cancerous and adjacent normal tissues from patients with GC were detected using reverse transcription‑quantitative polymerase chain reaction. The clinical relevance was then statistically analyzed. The results revealed the overexpression of the three miRNAs, miR‑21, miR‑223 and miR‑19, in tumor tissues compared to the corresponding normal tissues. In addition, the upregulation of the mentioned miRNAs in GC tissues was also significantly associated with Epstein‑Barr virus and H. pylori infections, as well as with aggressive clinicopathological features. On the whole, the findings of the present study indicate the potential of miR‑21, miR‑223 and miR‑19 for use as novel diagnostic, prognostic and predictive biomarkers for gastric tumors. However, further randomized studies involving diverse populations and functional assessments are required to extend and confirm these findings.

View Figures

View References

1	Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015.PubMed/NCBI View Article : Google Scholar
2	Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021.PubMed/NCBI View Article : Google Scholar
3	Konturek PC, Konturek SJ and Brzozowski T: Helicobacter pylori infection in gastric cancerogenesis. J Physiol Pharmacol. 60:3–21. 2009.PubMed/NCBI
4	Thompson MP and Kurzrock R: Epstein-Barr virus and cancer. Clin Cancer Res. 10:803–821. 2004.PubMed/NCBI View Article : Google Scholar
5	Fuccio L, Eusebi LH and Bazzoli F: Gastric cancer, Helicobacter pylori infection and other risk factors. World J Gastrointest Oncol. 2:342–347. 2010.PubMed/NCBI View Article : Google Scholar
6	Ali Syeda Z, Langden SSS, Munkhzul C, Lee M and Song SJ: Regulatory mechanism of microRNA expression in cancer. Int J Mol Sci. 21(1723)2020.PubMed/NCBI View Article : Google Scholar
7	Hussen BM, Hidayat HJ, Salihi A, Sabir DK, Taheri M and Ghafouri-Fard S: MicroRNA: A signature for cancer progression. Biomed Pharmacother. 138(111528)2021.PubMed/NCBI View Article : Google Scholar
8	Arif KMT, Elliott EK, Haupt LM and Griffiths LR: Regulatory mechanisms of epigenetic miRNA relationships in human cancer and potential as therapeutic targets. Cancers (Basel). 12(2922)2020.PubMed/NCBI View Article : Google Scholar
9	Lytle JR, Yario TA and Steitz JA: Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5'UTR as in the 3'UTR. Proc Natl Acad Sci USA. 104:9667–9672. 2007.PubMed/NCBI View Article : Google Scholar
10	Behm-Ansmant I, Rehwinkel J, Doerks T, Stark A, Bork P and Izaurralde E: mRNA degradation by miRNAs and GW182 requires both CCR4:NOT deadenylase and DCP1:DCP2 decapping complexes. Genes Dev. 20:1885–1898. 2006.PubMed/NCBI View Article : Google Scholar
11	Catalanotto C, Cogoni C and Zardo G: MicroRNA in control of gene expression: An overview of nuclear functions. Int J Mol Sci. 17(1712)2016.PubMed/NCBI View Article : Google Scholar
12	Alvarez-Garcia I and Miska EA: MicroRNA functions in animal development and human disease. Development. 132:4653–4662. 2005.PubMed/NCBI View Article : Google Scholar
13	Miska EA: How microRNAs control cell division, differentiation and death. Curr Opin Genet Dev. 15:563–568. 2005.PubMed/NCBI View Article : Google Scholar
14	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004.PubMed/NCBI View Article : Google Scholar
15	Croce CM and Calin GA: miRNAs, cancer, and stem cell division. Cell. 122:6–7. 2005.PubMed/NCBI View Article : Google Scholar
16	Gregory RI and Shiekhattar R: MicroRNA biogenesis and cancer. Cancer Res. 65:3509–3512. 2005.PubMed/NCBI View Article : Google Scholar
17	Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, et al: A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA. 103:2257–2261. 2006.PubMed/NCBI View Article : Google Scholar
18	Petrocca F, Visone R, Onelli MR, Shah MH, Nicoloso MS, de Martino I, Iliopoulos D, Pilozzi E, Liu CG, Negrini M, et al: E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell. 13:272–286. 2008.PubMed/NCBI View Article : Google Scholar
19	Kozomara A, Birgaoanu M and Griffiths-Jones S: miRBase: From microRNA sequences to function. Nucleic Acids Res. 47:D155–D162. 2019.PubMed/NCBI View Article : Google Scholar
20	Yuan C, Zhang Y, Tu W and Guo Y: Integrated miRNA profiling and bioinformatics analyses reveal upregulated miRNAs in gastric cancer. Oncol Lett. 18:1979–1988. 2019.PubMed/NCBI View Article : Google Scholar
21	Irmak-Yazicioglu MB: Mechanisms of microRNA deregulation and microRNA targets in gastric cancer. Oncol Res Treatment. 39:136–139. 2016.PubMed/NCBI View Article : Google Scholar
22	Liu L, Zhao Y, Fan G, Shuai T, Li B and Li Y: Helicobacter pylori infection enhances heparanase leading to cell proliferation via mitogen-activated protein kinase signalling in human gastric cancer cells. Mol Med Rep. 18:5733–5741. 2018.PubMed/NCBI View Article : Google Scholar
23	Ding N, Zou Z, Sha H, Su S, Qian H, Meng F, Chen F, Du S, Zhou S, Chen H, et al: iRGD synergizes with PD-1 knockout immunotherapy by enhancing lymphocyte infiltration in gastric cancer. Nat Commun. 10(1336)2019.PubMed/NCBI View Article : Google Scholar
24	Prinz C, Mese K and Weber D: MicroRNA Changes in gastric carcinogenesis: Differential dysregulation during Helicobacter pylori and EBV Infection. Genes. 12(597)2021.PubMed/NCBI View Article : Google Scholar
25	Săsăran MO, Meliț LE and Dobru ED: Microrna modulation of host immune response and inflammation triggered by Helicobacter pylori. Int J Mol Sci. 22(1406)2021.PubMed/NCBI View Article : Google Scholar
26	Iizasa H, Kim H, Kartika AV, Kanehiro Y and Yoshiyama H: Role of viral and host microRNAs in immune regulation of Epstein-Barr virus-associated diseases. Front Immunol. 11(367)2020.PubMed/NCBI View Article : Google Scholar
27	Lu JJ, Perng CL, Shyu RY, Chen CH, Lou Q, Chong SK and Lee CH: Comparison of five PCR methods for detection of Helicobacter pylori DNA in gastric tissues. J Clin Microbiol. 37:772–774. 1999.PubMed/NCBI View Article : Google Scholar
28	Ortiz-Princz D, Guariglia-Oropeza V, Avila M, Correnti M, Perrone M, Gutierrez B, Torres J, Megraud F and Cavazza ME: Helicobacter pylori cagA and vacA genotypes in Cuban and Venezuelan populations. Mem Inst Oswaldo Cruz. 105:331–335. 2010.PubMed/NCBI View Article : Google Scholar
29	Lu H, Zhu C, Li F, Xu W, Tao D and Feng X: Putative periodontopathic bacteria and herpesviruses in pregnant women: A case-control study. Sci Rep. 6(27796)2016.PubMed/NCBI View Article : Google Scholar
30	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
31	Ebert MP and Röcken C: Molecular screening of gastric cancer by proteome analysis. Eur J Gastroenterol Hepatol. 18:847–853. 2006.PubMed/NCBI View Article : Google Scholar
32	Liu X, Cai H and Wang Y: Prognostic significance of tumour markers in Chinese patients with gastric cancer. ANZ J Surg. 84:448–453. 2014.PubMed/NCBI View Article : Google Scholar
33	Wang D, Fan Z, Liu F and Zuo J: Hsa-miR-21 and Hsa-miR-29 in tissue as potential diagnostic and prognostic biomarkers for gastric cancer. Cell Physiol Biochem. 37:1454–1462. 2015.PubMed/NCBI View Article : Google Scholar
34	Emami SS, Nekouian R, Akbari A, Faraji A, Abbasi V and Agah S: Evaluation of circulating miR-21 and miR-222 as diagnostic biomarkers for gastric cancer. J Cancer Res Ther. 15:115–119. 2019.PubMed/NCBI View Article : Google Scholar
35	Zhang Z, Li Z, Gao C, Chen P, Chen J, Liu W, Xiao S and Lu H: miR-21 plays a pivotal role in gastric cancer pathogenesis and progression. Lab Invest. 88:1358–1366. 2008.PubMed/NCBI View Article : Google Scholar
36	Du YY, Dai DQ and Yang Z: Role of RECK methylation in gastric cancer and its clinical significance. World J Gastroenterol. 16:904–908. 2010.PubMed/NCBI View Article : Google Scholar
37	Zhao H, Wang Y, Yang L, Jiang R and Li W: MiR-25 promotes gastric cancer cells growth and motility by targeting RECK. Mol Cell Biochem. 385:207–213. 2014.PubMed/NCBI View Article : Google Scholar
38	Li J, Guo Y, Liang X, Sun M, Wang G, De W and Wu W: MicroRNA-223 functions as an oncogene in human gastric cancer by targeting FBXW7/hCdc4. J Cancer Res Clin Oncol. 138:763–774. 2012.PubMed/NCBI View Article : Google Scholar
39	Ueda T, Volinia S, Okumura H, Shimizu M, Taccioli C, Rossi S, Alder H, Liu CG, Oue N, Yasui W, et al: Relation between microRNA expression and progression and prognosis of gastric cancer: A microRNA expression analysis. Lancet Oncol. 11:136–146. 2010.PubMed/NCBI View Article : Google Scholar
40	Qin S, Ai F, Ji WF, Rao W, Zhang HC and Yao WJ: miR-19a promotes cell growth and tumorigenesis through targeting SOCS1 in gastric cancer. Asian Pac J Cancer Prev. 14:835–840. 2013.PubMed/NCBI View Article : Google Scholar
41	Chang H, Kim N, Park JH, Nam RH, Choi YJ, Lee HS, Yoon H, Shin CM, Park YS, Kim JM and Lee DH: Different microRNA expression levels in gastric cancer depending on Helicobacter pylori infection. Gut Liver. 9:188–196. 2015.PubMed/NCBI View Article : Google Scholar
42	Riley KJ, Rabinowitz GS, Yario TA, Luna JM, Darnell RB and Steitz JA: EBV and human microRNAs co-target oncogenic and apoptotic viral and human genes during latency. EMBO J. 31:2207–2221. 2012.PubMed/NCBI View Article : Google Scholar
43	Zheng Q, Chen C, Guan H, Kang W and Yu C: Prognostic role of microRNAs in human gastrointestinal cancer: A systematic review and meta-analysis. Oncotarget. 8:46611–46623. 2017.PubMed/NCBI View Article : Google Scholar
44	Sun X, Zhang K and Li D: Prognostic potential of miR-21-3p in gastric cancer. J BUON. 25:2678–2682. 2020.PubMed/NCBI