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01-12-2020 | Helicobacter Pylori | Research article

Fluctuating expression of miR-584 in primary and high-grade gastric cancer

Authors: Laleh Ebrahimi Ghahnavieh, Hossein Tabatabaeian, Zhaleh Ebrahimi Ghahnavieh, Mohammad Amin Honardoost, Mansoureh Azadeh, Mohamad Moazeni Bistgani, Kamran Ghaedi

Published in: BMC Cancer | Issue 1/2020

Abstract

Background

Gastric cancer is the fifth most common cancer worldwide. Along with environmental factors, such as Helicobacter pylori (H. pylori) infection, genetic changes play important roles in gastric tumor formations. miR-584 is a less well-characterized microRNA (miRNA), with apparent activity in human cancers. However, miR-584 expression pattern in gastric cancer development has remained unclear. This study aims to analyze the expression of miR-584 in gastric cancer samples and investigates the associations between this miRNA and H. pylori infection and clinical characteristics.

Methods

The expression level of miR-584 was studied in primary gastric cancers versus healthy control gastric mucosa samples using the RT-qPCR method. The clinical data were analyzed statistically in terms of miR-584 expression. In silico studies were employed to study miR-584 more broadly in order to assess its expression and find new potential target genes.

Results

Both experimental and in silico studies showed up-regulation of miR-584 in patients with gastric cancer. This up-regulation seems to be induced by H. pylori infection since the infected samples showed increased levels of miR-584 expression. Deeper analyses revealed that miR-584 undergoes a dramatic down-regulation in late stages, invasive and lymph node-metastatic gastric tumors. Bioinformatics studies demonstrated that miR-584 has a substantial role in cancer pathways and has the potential to target STAT1 transcripts. Consistent with the inverse correlation between TCGA RNA-seq data of miR-584 and STAT1 transcripts, the qPCR analysis showed a significant negative correlation between these two RNAs in a set of clinical samples.

Conclusion

miR-584 undergoes up-regulation in the stage of primary tumor formation; however, becomes down-regulated upon the progression of gastric cancer. These findings suggest the potential of miR-584 as a diagnostic or prognostic biomarker in gastric cancer.

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Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.PubMed

Arnold M, Karim-Kos HE, Coebergh JW, Byrnes G, Antilla A, Ferlay J, Renehan AG, Forman D, Soerjomataram I. Recent trends in incidence of five common cancers in 26 European countries since 1988: Analysis of the European Cancer observatory. Eur J Cancer. 2013;51(9):1164-87.

Park B, Shin A, Park SK, Ko K-P, Ma SH, Lee E-H, Gwack J, Jung E-J, Cho LY, Yang JJ. Ecological study for refrigerator use, salt, vegetable, and fruit intakes, and gastric cancer. Cancer Causes Control. 2011;22(11):1497.PubMedCrossRef

Kuipers E. Review article: exploring the link between helicobacter pylori and gastric cancer. Aliment Pharmacol Ther. 1999;13(s1):3–11.PubMedCrossRef

Suerbaum S, Michetti P. Helicobacter pylori infection. N Engl J Med. 2002;347(15):1175–86.PubMedCrossRef

Adami B, Tabatabaeian H, Ghaedi K, Talebi A, Azadeh M, Dehdashtian E. miR-146a is deregulated in gastric cancer. J Cancer Res Ther. 2019;15(1):108.PubMed

Noormohammad M, Sadeghi S, Tabatabaeian H, Ghaedi K, Talebi A, Azadeh M, Khatami M, Heidari MM. Upregulation of miR-222 in both helicobacter pylori-infected and noninfected gastric cancer patients. J Genet. 2016;95(4):991–5.PubMedCrossRef

Hao N-B, He Y-F, Li X-Q, Wang K, Wang R-L. The role of miRNA and lncRNA in gastric cancer. Oncotarget. 2017;8(46):81572.PubMedPubMedCentralCrossRef

Dehdashtian E, Tabatabaeian H, Ghaedi K, Talebi A, Adami B. A H. pylori-independent miR-21 overexpression in gastric cancer patients. Gene Reports. 2019;17:100528.

10.

Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215–33.PubMedPubMedCentralCrossRef

11.

da Silva Oliveira KC, Araújo TMT, Albuquerque CI, Barata GA, Gigek CO, Leal MF, Wisnieski F, Junior FARM, Khayat AS, de Assumpção PP. Role of miRNAs and their potential to be useful as diagnostic and prognostic biomarkers in gastric cancer. World J Gastroenterol. 2016;22(35):7951.PubMedPubMedCentralCrossRef

12.

Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA. MicroRNA expression profiles classify human cancers. Nature. 2005;435(7043):834–8.PubMedCrossRef

13.

Oertli M, Engler DB, Kohler E, Koch M, Meyer TF, Müller A. MicroRNA-155 is essential for the T cell-mediated control of helicobacter pylori infection and for the induction of chronic gastritis and colitis. J Immunol. 2011;187(7):3578–86.PubMedCrossRef

14.

Chen L, Yang Q, Kong WQ, Liu T, Liu M, Li X, Tang H. MicroRNA-181b targets cAMP responsive element binding protein 1 in gastric adenocarcinomas. IUBMB Life. 2012;64(7):628–35.PubMedCrossRef

15.

Baud J, Varon C, Chabas S, Chambonnier L, Darfeuille F, Staedel C. Helicobacter pylori initiates a mesenchymal transition through ZEB1 in gastric epithelial cells. PLoS One. 2013;8(4):e60315.PubMedPubMedCentralCrossRef

16.

Liu X, Ru J, Zhang J, L-h Z, Liu M, Li X, Tang H. miR-23a targets interferon regulatory factor 1 and modulates cellular proliferation and paclitaxel-induced apoptosis in gastric adenocarcinoma cells. PLoS One. 2013;8(6):e64707.PubMedPubMedCentralCrossRef

17.

Baltimore D, Boldin MP, O'Connell RM, Rao DS, Taganov KD. MicroRNAs: new regulators of immune cell development and function. Nat Immunol. 2008;9(8):839–45.PubMedCrossRef

18.

Zhang Z, Li Z, Gao C, Chen P, Chen J, Liu W, Xiao S, Lu H. miR-21 plays a pivotal role in gastric cancer pathogenesis and progression. Lab Investig. 2008;88(12):1358–66.PubMedCrossRef

19.

Belair C, Darfeuille F, Staedel C. Helicobacter pylori and gastric cancer: possible role of microRNAs in this intimate relationship. Clin Microbiol Infect. 2009;15(9):806–12.PubMedCrossRef

20.

Matsushima K, Isomoto H, Inoue N, Nakayama T, Hayashi T, Nakayama M, Nakao K, Hirayama T, Kohno S. MicroRNA signatures in helicobacter pylori-infected gastric mucosa. Int J Cancer. 2011;128(2):361–70.PubMedCrossRef

21.

Zhou L, Zhao X, Han Y, Lu Y, Shang Y, Liu C, Li T, Jin Z, Fan D, Wu K. Regulation of UHRF1 by miR-146a/b modulates gastric cancer invasion and metastasis. FASEB J. 2013;27(12):4929–39.PubMedCrossRef

22.

Xiao B, Liu Z, Li B-S, Tang B, Li W, Guo G, Shi Y, Wang F, Wu Y, Tong W-D. 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.PubMedCrossRef

23.

Shiotani A, Uedo N, Iishi H, Murao T, Kanzaki T, Kimura Y, Kamada T, Kusunoki H, Inoue K, Haruma K. H. Pylori eradication did not improve dysregulation of specific oncogenic miRNAs in intestinal metaplastic glands. J Gastroenterol. 2012;47(9):988–98.PubMedCrossRef

24.

Isomoto H, Matsushima K, Inoue N, Hayashi T, Nakayama T, Kunizaki M, Hidaka S, Nakayama M, Hisatsune J, Nakashima M. Interweaving microRNAs and proinflammatory cytokines in gastric mucosa with reference to H. pylori infection. J Clin Immunol. 2012;32(2):290–9.PubMedCrossRef

25.

Li N, Tang B, Zhu E-D, B-s L, Zhuang Y, Yu S, D-s L, Zou Q-M, Xiao B, Mao X-H. Increased miR-222 in H. pylori-associated gastric cancer correlated with tumor progression by promoting cancer cell proliferation and targeting RECK. FEBS Lett. 2012;586(6):722–8.PubMedCrossRef

26.

Zhu Y, Jiang Q, Lou X, Ji X, Wen Z, Wu J, Tao H, Jiang T, He W, Wang C. MicroRNAs up-regulated by CagA of helicobacter pylori induce intestinal metaplasia of gastric epithelial cells. PLoS One. 2012;7(4):e35147.PubMedPubMedCentralCrossRef

27.

G-g T, Wang W-h, Dai Y, S-j W, Y-x C, Li J. let-7b is involved in the inflammation and immune responses associated with helicobacter pylori infection by targeting toll-like receptor 4. PLoS One. 2013;8(2):e56709.CrossRef

28.

Feng Y, Wang L, Zeng J, Shen L, Liang X, Yu H, Liu S, Liu Z, Sun Y, Li W. FoxM1 is overexpressed in helicobacter pylori–induced gastric carcinogenesis and is negatively regulated by miR-370. Mol Cancer Res. 2013;11(8):834–44.PubMedCrossRef

29.

Belair C, Baud J, Chabas S, Sharma CM, Vogel J, Staedel C, Darfeuille F. Helicobacter pylori interferes with an embryonic stem cell micro RNA cluster to block cell cycle progression. Silence. 2011;2(1):7.PubMedPubMedCentralCrossRef

30.

Kheir TB, Futoma-Kazmierczak E, Jacobsen A, Krogh A, Bardram L, Hother C, Grønbæk K, Federspiel B, Lund AH, Friis-Hansen L. miR-449 inhibits cell proliferation and is down-regulated in gastric cancer. Mol Cancer. 2011;10(1):1.CrossRef

31.

Li Q, Li Z, Wei S, Wang W, Chen Z, Zhang L, Chen L, Li B, Sun G, Xu J. Overexpression of miR-584-5p inhibits proliferation and induces apoptosis by targeting WW domain-containing E3 ubiquitin protein ligase 1 in gastric cancer. J Exp Clin Cancer Res. 2017;36(1):59.PubMedPubMedCentralCrossRef

32.

Li J-H, Liu S, Zhou H, Qu L-H, Yang J-H. starBase v2. 0: decoding miRNA-ceRNA, miRNA-ncRNA and protein–RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 2013;42(D1):D92–7.PubMedPubMedCentralCrossRef

33.

Nagy Á, Lánczky A, Menyhárt O, Győrffy B. Validation of miRNA prognostic power in hepatocellular carcinoma using expression data of independent datasets. Sci Rep. 2018;8(1):9227.PubMedPubMedCentralCrossRef

34.

Dweep H, Gretz N. miRWalk2. 0: a comprehensive atlas of microRNA-target interactions. Nature methods. 2015;12(8):697.

35.

Hsu S-D, Tseng Y-T, Shrestha S, Lin Y-L, Khaleel A, Chou C-H, Chu C-F, Huang H-Y, Lin C-M, Ho S-Y. miRTarBase update 2014: an information resource for experimentally validated miRNA-target interactions. Nucleic Acids Res. 2014;42(D1):D78–85.PubMedCrossRef

36.

Chou C-H, Chang N-W, Shrestha S, Hsu S-D, Lin Y-L, Lee W-H, Yang C-D, Hong H-C, Wei T-Y, Tu S-J. miRTarBase 2016: updates to the experimentally validated miRNA-target interactions database. Nucleic Acids Res. 2015:gkv1258.

37.

Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4(1):44.CrossRef

38.

Kanehisa M, Goto S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 2000;28(1):27–30.PubMedPubMedCentralCrossRef

39.

Jin SP, Kim JH, Kim MA, Yang H-K, Lee HE, Lee HS, Kim WH. Prognostic significance of loss of c-fos protein in gastric carcinoma. Pathol Oncol Res. 2007;13(4):284–9.PubMedCrossRef

40.

Peng Y, Zhang P, Huang X, Yan Q, Wu M, Xie R, Wu Y, Zhang M, Nan Q, Zhao J. Direct regulation of FOXK1 by C-Jun promotes proliferation, invasion and metastasis in gastric cancer cells. Cell Death Dis. 2016;7(11):–e2480.

41.

Zhang C, Cleveland K, Schnoll-Sussman F, McClure B, Bigg M, Thakkar P, Schultz N, Shah MA, Betel D. Identification of low abundance microbiome in clinical samples using whole genome sequencing. Genome Biol. 2015;16(1):265.PubMedPubMedCentralCrossRef

42.

Hu L, Ai J, Long H, Liu W, Wang X, Zuo Y, Li Y, Wu Q, Deng Y. Integrative microRNA and gene profiling data analysis reveals novel biomarkers and mechanisms for lung cancer. Oncotarget. 2016;7(8):8441–54.PubMedPubMedCentralCrossRef

43.

Fils-Aimé N, Dai M, Guo J, El-Mousawi M, Kahramangil B, Neel J-C, Lebrun J-J. MicroRNA-584 and the protein phosphatase and actin regulator 1 (PHACTR1), a new signaling route through which transforming growth factor-β mediates the migration and actin dynamics of breast cancer cells. J Biol Chem. 2013;288(17):11807–23.PubMedPubMedCentralCrossRef

44.

Xiang X, Mei H, Qu H, Zhao X, Li D, Song H, Jiao W, Pu J, Huang K, Zheng L. miRNA-584-5p exerts tumor suppressive functions in human neuroblastoma through repressing transcription of matrix metalloproteinase 14. Biochim Biophys Acta. 2015;1852(9):1743–54.PubMedCrossRef

45.

Sepulveda A, Tao H, Carloni E, Sepulveda J, Graham D, Peterson L. Screening of gene expression profiles in gastric epithelial cells induced by helicobacter pylori using microarray analysis. Aliment Pharmacol Ther. 2002;16:145–57.PubMedCrossRef

46.

Meyer-ter-Vehn T, Covacci A, Kist M, Pahl HL. Helicobacter pylori activates mitogen-activated protein kinase cascades and induces expression of the proto-oncogenes c-fos and c-Jun. J Biol Chem. 2000;275(21):16064–72.PubMedCrossRef

47.

Narasimhan K, Gauthaman K, Pushparaj PN, Meenakumari G, Chaudhary AGA, Abuzenadah A, Gari MA, Al Qahtani M, Manikandan J. Identification of unique miRNA biomarkers in colorectal adenoma and carcinoma using microarray: evaluation of their putative role in disease progression. ISRN Cell Biol. 2014;2014:1-10.

48.

Ouhara K, Savitri IJ, Fujita T, Kittaka M, Kajiya M, Iwata T, Miyagawa T, Yamakawa M, Shiba H, Kurihara H. miR-584 expressed in human gingival epithelial cells is induced by Porphyromonas gingivalis stimulation and regulates interleukin-8 production via lactoferrin receptor. J Periodontol. 2014;85(6):e198–204.PubMedCrossRef

49.

Zhong S, Zhang S, Bair E, Nares S, Khan AA. Differential expression of microRNAs in normal and inflamed human pulps. J Endod. 2012;38(6):746–52.PubMedCrossRef

50.

Xiang J, Wu Y, Li D-S, Wang Z-Y, Shen Q, Sun T-Q, Guan Q, Wang Y-J. miR-584 suppresses invasion and cell migration of thyroid carcinoma by regulating the target oncogene ROCK1. Oncol Res Treat. 2015;38(9):436–40.PubMedCrossRef

Title: Fluctuating expression of miR-584 in primary and high-grade gastric cancer
Authors: Laleh Ebrahimi Ghahnavieh
Hossein Tabatabaeian
Zhaleh Ebrahimi Ghahnavieh
Mohammad Amin Honardoost
Mansoureh Azadeh
Mohamad Moazeni Bistgani
Kamran Ghaedi
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Helicobacter Pylori
Gastric Cancer
Gastric Cancer
Published in: BMC Cancer / Issue 1/2020
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-020-07116-5

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