Screening and identification of differentially expressed microRNAs in diffuse large B‑cell lymphoma based on microRNA microarray

Gao,Hai-Xia; Li,Si-Jing; Wang,Meng-Bo; Yan,Shu-Fang; Cui,Wen-Li; Ma,Zhi-Ping; Xue,Jing; Sang,Wei; Zhang,Wei; Li,Xin-Xia

doi:10.3892/ol.2021.13014

Screening and identification of differentially expressed microRNAs in diffuse large B‑cell lymphoma based on microRNA microarray

Authors:
- Hai-Xia Gao
- Si-Jing Li
- Meng-Bo Wang
- Shu-Fang Yan
- Wen-Li Cui
- Zhi-Ping Ma
- Jing Xue
- Wei Sang
- Wei Zhang
- Xin-Xia Li
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Affiliations: Department of Pathology and NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, Xinjiang Uygur Autonomous Region 832002, P.R. China, Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Ürümqi, Xinjiang Uygur Autonomous Region 830054, P.R. China, Department of Ultrasound, The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, Xinjiang Uygur Autonomous Region 832002, P.R. China
Published online on: August 27, 2021 https://doi.org/10.3892/ol.2021.13014
Article Number: 753
Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Diffuse large B‑cell lymphoma (DLBCL) is the most common type of B‑cell non‑Hodgkin lymphoma in adults and the pathogenesis of DLBCL is multifactorial and complex. Understanding the molecular mechanisms involved in DLBCL is important to identify new therapeutic targets. The present study aimed to screen and identify differentially expressed microRNAs (miRNAs/miRs) between diffuse large B‑cell lymphoma (DLBCL) and control [lymph node reactive hyperplasia (LRH)] groups, and to investigate whether miRNAs associated with DLBCL could serve as potential therapeutic targets. In total, 5 DLBCL experimental samples and 5 control samples were obtained from fresh patient tissues. Firstly, the fresh samples were analyzed using miRNA microarray to identify differentially expressed miRNAs. Next, three databases (TargetScan, microRNA.org and PITA) were used to predict by intersection the potential target genes of the 204 differential miRNAs identified, and a Venn diagram of the results was performed. Subsequently, the target genes of differential miRNAs were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Finally, to validate the miRNA microarray data, reverse transcription‑quantitative PCR (RT‑qPCR) was performed for 8 differentially expressed miRNAs (miR‑193a‑3p, miR‑19a‑3p, miR‑19b‑3p, miR‑370‑3p, miR‑1275, miR‑490‑5p, miR‑630 and miR‑665) using DLBCL and LRH fresh samples. In total, 204 miRNAs exhibited differential expression, including 105 downregulated and 54 upregulated miRNAs. The cut‑off criteria were set as P≤0.05 and fold‑change ≥2. A total of 7,522 potential target genes for the 204 miRNAs were predicted. Potential target genes were enriched in the following pathways: ‘Cancer’, ‘MAPK signaling pathway’, ‘regulation of actin cytoskeleton’, ‘focal adhesion’, ‘endocytosis’, ‘Wnt signaling pathway’, ‘axon guidance’, ‘calcium signaling pathway’ and ‘PI3K/AKT signaling pathway’. A total of 8 miRNAs were validated by RT‑qPCR, and 4 miRNAs (miR‑19b‑3p, miR‑193a‑3p, miR‑370‑3p and miR‑490‑5p) exhibited low expression levels in DLBCL (P<0.05), while miR‑630 was highly expressed in DLBCL (P<0.05). Overall, the present study screened 204 differentially expressed miRNAs and analyzed the expression levels of 8 differentially expressed miRNAs in DLBCL. These differentially expressed miRNAs may serve as therapeutic targets for improvement of therapeutic efficacy in DLBCL in the future.

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1	Li S, Young KH and Medeiros LJ: Diffuse large B-cell lymphoma. Pathology. 50:74–87. 2018. View Article : Google Scholar : PubMed/NCBI
2	Roschewski M, Staudt LM and Wilson WH: Diffuse large B-cell lymphoma-treatment approaches in the molecular era. Nat Rev Clin Oncol. 11:12–23. 2014. View Article : Google Scholar : PubMed/NCBI
3	Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, Müller-Hermelink HK, Campo E, Braziel RM, Jaffe ES, et al: Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 103:275–282. 2004. View Article : Google Scholar : PubMed/NCBI
4	Coiffier B and Sarkozy C: Diffuse large B-cell lymphoma: R-CHOP failure-what to do? Hematology Am Soc Hematol Educ Program. 2016:366–378. 2016. View Article : Google Scholar : PubMed/NCBI
5	Gao HX, Nuerlan A, Abulajiang G, Cui WL, Xue J, Sang W, Li SJ, Niu J, Ma ZP, Zhang W and Li XX: Quantitative proteomics analysis of differentially expressed proteins in activated B-cell-like diffuse large B-cell lymphoma using quantitative proteomics. Pathol Res Pract. 215:1525282019. View Article : Google Scholar : PubMed/NCBI
6	Gao HX, Li SJ, Niu J, Ma ZP, Nuerlan A, Xue J, Wang MB, Cui WL, Abulajiang G, Sang W, et al: TCL1 as a hub protein associated with the PI3K/AKT signaling pathway in diffuse large B-cell lymphoma based on proteomics methods. Pathol Res Pract. 216:1527992020. View Article : Google Scholar : PubMed/NCBI
7	Liu Z, Wang Y, Shu S, Cai J, Tang C and Dong Z: Non-coding RNAs in kidney injury and repair. Am J Physiol Cell Physiol. 317:C177–C188. 2019. View Article : Google Scholar : PubMed/NCBI
8	Baronti L, Guzzetti I, Ebrahimi P, Friebe Sandoz S, Steiner E, Schlagnitweit J, Fromm B, Silva L, Fontana C, Chen AA and Petzold K: Base-pair conformational switch modulates miR-34a targeting of Sirt1 mRNA. Nature. 583:139–144. 2020. View Article : Google Scholar : PubMed/NCBI
9	Lee RC, Feinbaum RL and Ambros V: The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 75:843–854. 1993. View Article : Google Scholar : PubMed/NCBI
10	Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, et al: WHO classification of tumours of haematopoetic and lymphoid tissues. 4th edition. IARC Press; Lyon: 2017
11	Felix TF, Lopez Lapa RM, de Carvalho M, Bertoni N, Tokar T, Oliveira RA, M Rodrigues MA, Hasimoto CN, Oliveira WK, Pelafsky L, et al: MicroRNA modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma. PLoS One. 14:e02174212019. View Article : Google Scholar : PubMed/NCBI
12	Xue J, Gao HX, Sang W, Cui WL, Liu M, Zhao Y, Wang MB, Wang Q and Zhang W: Identification of core differentially methylated genes in glioma. Oncol Lett. 18:6033–6045. 2019.PubMed/NCBI
13	Hu S, Zheng Q, Wu H, Wang C, Liu T and Zhou W: miR-532 promoted gastric cancer migration and invasion by targeting NKD1. Life Sci. 177:15–19. 2017. View Article : Google Scholar : PubMed/NCBI
14	Kakurina GV, Kolegova ES, Shashova EE, Cheremisina OV, Choynzonov EL and Kondakova IV: Relationship between the mRNA expression levels of calpains 1/2 and proteins involved in cytoskeleton remodeling. Acta Naturae. 12:110–113. 2020. View Article : Google Scholar : PubMed/NCBI
15	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. View Article : Google Scholar : PubMed/NCBI
16	Due H, Brøndum RF, Young KH, Bøgsted M and Dybkær K: MicroRNAs associated to single drug components of R-CHOP identifies diffuse large B-cell lymphoma patients with poor outcome and adds prognostic value to the international prognostic index. BMC Cancer. 20:2372020. View Article : Google Scholar : PubMed/NCBI
17	Li L, Lei Q, Zhang S, Kong L and Qin B: Screening and identification of key biomarkers in hepatocellular carcinoma: Evidence from bioinformatic analysis. Oncol Rep. 38:2607–2618. 2017. View Article : Google Scholar : PubMed/NCBI
18	Khordadmehr M, Shahbazi R, Sadreddini S and Baradaran B: miR-193: A new weapon against cancer. J Cell Physiol. 234:16861–16872. 2019. View Article : Google Scholar : PubMed/NCBI
19	Musilova K and Mraz M: MicroRNAs in B-cell lymphomas: How a complex biology gets more complex. Leukemia. 29:1004–1017. 2015. View Article : Google Scholar : PubMed/NCBI
20	Beheshti A, Stevenson K, Vanderburg C, Ravi D, McDonald JT, Christie AL, Shigemori K, Jester H, Weinstock DM and Evens AM: Identification of circulating serum multi-MicroRNA signatures in human DLBCL models. Sci Rep. 9:171612019. View Article : Google Scholar : PubMed/NCBI
21	Ting CY, Liew SM, Price A, Gan GG, Bee-Lan Ong D, Tan SY and Bee PC: Clinical significance of aberrant microRNAs expression in predicting disease relapse/refractoriness to treatment in diffuse large B-cell lymphoma: A meta-analysis. Crit Rev Oncol Hematol. 144:1028182019. View Article : Google Scholar : PubMed/NCBI
22	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
23	Yoon S, Nguyen HCT, Jo W, Kim J, Chi SM, Park J, Kim SY and Nam D: Biclustering analysis of transcriptome big data identifies condition-specific microRNA targets. Nucleic Acids Res. 47:e532019. View Article : Google Scholar : PubMed/NCBI
24	Shim H, Nam J and Kim SW: NF-κB p65 represses microRNA-124 transcription in diffuse large B-cell lymphoma. Genes Genomics. 42:543–551. 2020. View Article : Google Scholar : PubMed/NCBI
25	Zhao CC, Jiao Y, Zhang YY, Ning J, Zhang YR, Xu J, Wei W and Kang-Sheng G: Lnc SMAD5-AS1 as ceRNA inhibit proliferation of diffuse large B cell lymphoma via Wnt/β-catenin pathway by sponging miR-135b-5p to elevate expression of APC. Cell Death Dis. 10:2522019. View Article : Google Scholar : PubMed/NCBI
26	Tang Y, Yang J, Wang Y, Tang Z, Liu S and Tang Y: MiR-19b-3p facilitates the proliferation and epithelial-mesenchymal transition, and inhibits the apoptosis of intrahepatic cholangiocarcinoma by suppressing coiled-coil domain containing 6. Arch Biochem Biophys. 686:1083672020. View Article : Google Scholar : PubMed/NCBI
27	Park EJ, Jung HJ, Choi HJ, Jang HJ, Park HJ, Nejsum LN and Kwon TH: Exosomes co-expressing AQP5-targeting miRNAs and IL-4 receptor-binding peptide inhibit the migration of human breast cancer cells. FASEB J. 34:3379–3398. 2020. View Article : Google Scholar : PubMed/NCBI
28	Marcuello M, Duran-Sanchon S, Moreno L, Lozano JJ, Bujanda L, Castells A and Gironella M: Analysis of A 6-mirna signature in serum from colorectal cancer screening participants as non-invasive biomarkers for advanced adenoma and colorectal cancer detection. Cancers (Basel). 11:15422019. View Article : Google Scholar : PubMed/NCBI
29	Wang SS, Huang ZG, Wu HY, He RQ, Yang LH, Feng ZB, Dang YW, Lu HP, Fang YY and Chen G: Downregulation of miR-193a-3p is involved in the pathogenesis of hepatocellular carcinoma by targeting CCND1. PeerJ. 8:e84092020. View Article : Google Scholar : PubMed/NCBI
30	Lin M, Zhang Z, Gao M, Yu H, Sheng H and Huang J: MicroRNA-193a-3p suppresses the colorectal cancer cell proliferation and progression through downregulating the PLAU expression. Cancer Manag Res. 11:5353–5363. 2019. View Article : Google Scholar : PubMed/NCBI
31	Chen ZM, Yu Q, Chen G, Tang RX, Luo DZ, Dang YW and Wei DM: MiR-193a-3p inhibits pancreatic ductal adenocarcinoma cell proliferation by targeting CCND1. Cancer Manag Res. 11:4825–4837. 2019. View Article : Google Scholar : PubMed/NCBI
32	Li LM, Luo FJ and Song X: MicroRNA-370-3p inhibits cell proliferation and induces chronic myelogenous leukaemia cell apoptosis by suppressing PDLIM1/Wnt/β-catenin signaling. Neoplasma. 67:509–518. 2020. View Article : Google Scholar : PubMed/NCBI
33	Nadaradjane A, Briand J, Bougras-Cartron G, Disdero V, Vallette FM, Frenel JS and Cartron PF: miR-370-3p is a therapeutic tool in anti-glioblastoma therapy but is not an intratumoral or cell-free circulating biomarker. Mol Ther Nucleic Acids. 13:642–650. 2018. View Article : Google Scholar : PubMed/NCBI
34	Leivonen SK, Icay K, Jäntti K, Siren I, Liu C, Alkodsi A, Cervera A, Ludvigsen M, Hamilton-Dutoit SJ, d'Amore F, et al: MicroRNAs regulate key cell survival pathways and mediate chemosensitivity during progression of diffuse large B-cell lymphoma. Blood Cancer J. 7:6542017. View Article : Google Scholar : PubMed/NCBI
35	Wang J, Zhang X, Yao H, Le Y, Zhou W, Li J, Lu L, Chen M and Li X: MiR-490-5p functions as tumor suppressor in childhood neuroblastoma by targeting MYEOV. Hum Cell. 33:261–271. 2020. View Article : Google Scholar : PubMed/NCBI
36	Xiang M, Yuan W, Zhang W and Huang J: Expression of miR-490-5p, miR-148a-3p and miR-608 in bladder cancer and their effects on the biological characteristics of bladder cancer cells. Oncol Lett. 17:4437–4442. 2019.PubMed/NCBI
37	Valera VA, Parra-Medina R, Walter BA, Pinto P and Merino MJ: microRNA expression profiling in young prostate cancer patients. J Cancer. 11:4106–4114. 2020. View Article : Google Scholar : PubMed/NCBI
38	Pan XM, He XY, Yang YL, Jia WJ, Yang ZQ, Yan D and Ma JX: MiR-630 inhibits papillary thyroid carcinoma cell growth, metastasis, and epithelial-mesenchymal transition by suppressing JAK2/STAT3 signaling pathway. Eur Rev Med Pharmacol Sci. 23:2453–2460. 2019.PubMed/NCBI