A Bioinformatics Analysis of circRNA/miRNA/mRNA Interactions in Acute Myeloid Leukemia

Year 2023, Volume: 13 Issue: 1, 45 - 53, 11.05.2023

Cihat Erdoğan , Murat Kaya , Ilknur Suer

https://doi.org/10.26650/experimed.1227705

Abstract

Objective: Acute myeloid leukemia (AML) is a lethal type of cancer associated with dysregulation of progenitor hematopoietic stem cell behavior and its incidence is, unfortunately, increasing. Although there are various applications in treatment, since most of them are insufficient in early diagnosis, treatment and new prognostic biomarkers should be investigated.

Materials and Methods: In this study, three Gene Expression Omnibus (GEO) datasets Genomic Spatial Event (GSE); GSE94591, GSE116617, and GSE163386) were used to investigate dysregulated expressions of circular RNAs (circRNAs), and the GSE142699 and GSE142698 datasets were analyzed to detect dysregulated expressions of microRNAs (miRNAs) and mRNAs, respectively. Filtering was applied with p value <0.05, log2FC≥0.5 (circRNA), and log2FC≥1 (miRNA and mRNA) from the raw data analyzed using the limma R package (v.3.46.0). We investigated circRNA-miRNA-mRNA interactions using special tools including CSCDv2.0, circBank, miRTarBase, miRDB, multiMiR, miRWalk, DIANA-microT, TarBase, miRanda, and TargetScan. The pathway analysis was performed using KEGG and GO programs. The STRING database and Cytoscape tool were used to construct and view protein interaction. Hub gene analysis was constructed using the MCODE tool. We have utilized the GEPIA tool to determine the Overall Survival of the hub genes.

Results: In our study, 4 circRNAs, 3 miRNAs, and 6 genes that may be closely related to AML were detected.

Conclusion: According to our bioinformatics analysis results, hsa_circ_0012152/miR-199a-5p/HOXA9 axis could be more important in AML. Therefore, in vitro and in vivo investigations are recommended.

Keywords

Acute myeloid leukemia, circular RNA, bioinformatics

Supporting Institution

-

Project Number

-

Thanks

-

References

• 1. Kim TK, Gore SD, Zeidan AM. Epigenetic therapy in acute myeloid leukemia: Current and future directions. Semin Hematol 2015; 52(3):172-83. [CrossRef] google scholar
• 2. Zhang S, Liu M, Yao Y, Yu B, Liu H. Targeting LSD1 for acute myeloid leukemia (AML) treatment. Pharmacol Res 2021; 164: 105335. [CrossRef] google scholar
• 3. Kaya M, Suer I. The effect of miR-34a-5p on overexpressed AML associated genes. J Ist Faculty Med 2023; 86(1): 59-68. [CrossRef] google scholar
• 4. Voso MT, Ottone T, Lavorgna S, Venditti A, Maurillo L, Lo-Coco F, et al. MRD in AML: The role of new techniques. Front Oncol 2019; 9: 655. [CrossRef] google scholar
• 5. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin 2022; 72(1): 7-33. [CrossRef] google scholar
• 6. Capik O, Sanli F, Kurt A, Ceylan O, Suer I, Kaya M, et al. CASC11 promotes aggressiveness of prostate cancer cells through miR-145/IGF1R axis. Prostate Cancer Prostatic Dis 2021; 24(3): 891-902. [CrossRef] google scholar
• 7. Kaya M, Karatas OF. The relationship between larynx cancer and microRNAs. Van Med J 2020; 27(4): 535-41. [CrossRef] google scholar
• 8. Li X, Yang L, Chen LL. The biogenesis, functions, and challenges of circular RNAs. Mol Cell 2018; 71(3): 428-42. [CrossRef] google scholar
• 9. Cheng Y, Su Y, Wang S, Liu Y, Jin L, Wan Q, et al. Identification of circRNA-lncRNA-miRNA-mRNA competitive endogenous rna network as novel prognostic markers for acute myeloid leukemia. Genes (Basel) 2020; 11(8). [CrossRef] google scholar
• 10. Wu DM, Wen X, Han XR, Wang S, Wang YJ, Shen M, et al. Role of circular RNA DLEU2 in human acute myeloid leukemia. Mol Cell Biol 2018; 38(20). [CrossRef] google scholar
• 11. Wang N, Yang B, Jin J, He Y, Wu X, Yang Y, et al. Circular RNA circ_0040823 inhibits the proliferation of acute myeloid leukemia cells and induces apoptosis by regulating miR-516b/PTEN. J Gene Med 2022; 24(3): e3404. [CrossRef] google scholar
• 12. Suer I, Kaya M. Is the AURKB gene involved in aml cell proliferation since it is targeted by miR-34a-5p and let-7b-5p? Konuralp Medical Journal 2023; 15(1): 16-23 [CrossRef] google scholar
• 13. Guo S, Li B, Chen Y, Zou D, Yang S, Zhang Y, et al. Hsa_circ_0012152 and Hsa_circ_0001857 accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia. Front Oncol 2020; 10: 1655. [CrossRef] google scholar
• 14. Yan YY, Yang JT, Pathak JL, Wang HY, Zha J, Wei YX, et al. CircRNA_104889 promotes lung adenocarcinoma cell invasion via sponging miR4458. Cancer Cell International 2020; 20(1). [CrossRef] google scholar
• 15. Yang YR, Hu S, Bu FT, Li H, Huang C, Meng XM, et al. Circular RNA CREBBP suppresses hepatic fibrosis via targeting the hsa-miR-1291/LEFTY2 axis. Front Pharmacol 2021; 12: 741151. [CrossRef] google scholar
• 16. Shao Y, Li J, Lu R, Li T, Yang Y, Xiao B, et al. Global circular RNA expression profile of human gastric cancer and its clinical significance. Cancer Med 2017; 6(6): 1173-80. [CrossRef] google scholar
• 17. Jiang YM, Liu W, Jiang L, Chang H. CircLDLR promotes papillary thyroid carcinoma tumorigenicity by regulating miR-637/LMO4 Axis. Dis Markers 2021; 2021: 3977189. [CrossRef] google scholar
• 18. Jia Y, Li S, Zhang M, Zhang Z, Wang C, Zhang C, et al. Circ_LDLR knockdown suppresses progression of hepatocellular carcinoma via modulating miR-7/RNF38 axis. Cancer Manag Res 2021; 13: 337-49. [CrossRef] google scholar
• 19. Huang X, Wu B, Chen M, Hong L, Kong P, Wei Z, et al. Depletion of exosomal circLDLR in follicle fluid derepresses miR-1294 function and inhibits estradiol production via CYP19A1 in polycystic ovary syndrome. Aging (Albany NY). 2020; 12(15): 15414-35. [CrossRef] google scholar
• 20. Liao K, Qian Z, Zhang S, Chen B, Li Z, Huang R, et al. The LGMN pseudogene promotes tumor progression by acting as a miR-495-3p sponge in glioblastoma. Cancer Lett 2020; 490: 111-23. [CrossRef] google scholar
• 21. Esa E, Hashim AK, Mohamed EHM, Zakaria Z, Abu Hassan AN, Mat Yusoff Y, et al. Construction of a microRNA-mRNA regulatory network in de novo cytogenetically normal acute myeloid leukemia patients. Genet Test Mol Biomarkers 2021; 25(3): 199210. [CrossRef] google scholar
• 22. Bhavsar SP, L0kke C, Flægstad T, Einvik C. Hsa-miR-376c-3p targets Cyclin D1 and induces G1-cell cycle arrest in neuroblastoma cells. Oncol Lett 2018; 16(5): 6786-94. [CrossRef] google scholar
• 23. Ma X, Wen Y, Wang Y, Zhang M, Shi L, Wang C, et al. Linc00662 plays an oncogenic role in bladder cancer by sponging miR-199a-5p. Am J Transl Res 2021; 13(11): 12673-83. google scholar
• 24. Chen J, Hou SF, Tang FJ, Liu DS, Chen ZZ, Zhang HL, et al. HOTAIR/ Sp1/miR-199a critically regulates cancer stemness and malignant progression of cutaneous squamous cell carcinoma. Oncogene 2022; 41(1): 99-111. [CrossRef] google scholar
• 25. Li Y, Sun Y, Miao M, Shi X, Yang W, Liu ZG. [MiR-199a-5p Affects sensitivity of acute myeloid leukemia to adriamycin by targeting DRAM1]. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2020; 28(4): 1096104. google scholar
• 26. LiY, Zhang G, Wu B, Yang W, Liu Z. miR-199a-5p represses protective autophagy and overcomes chemoresistance by directly targeting DRAM1 in acute myeloid leukemia. J Oncol 2019; 2019: 5613417. [CrossRef] google scholar
• 27. Singh N, Bhakuni R, Chhabria D, Kirubakaran S. MDC1 depletion promotes cisplatin induced cell death in cervical cancer cells. BMC Res Notes 2020; 13(1): 146. [CrossRef] google scholar
• 28. Liu X, Dong R, Jiang Z, Wei Y, Li Y, Wei L, et al. MDC1 promotes ovarian cancer metastasis by inducing epithelial-mesenchymal transition. Tumour Biol 2015; 36(6): 4261-9. [CrossRef] google scholar
• 29. Ruff SE, Logan SK, Garabedian MJ, Huang TT. Roles for MDC1 in cancer development and treatment. DNA Repair (Amst). 2020; 95: 102948. [CrossRef] google scholar
• 30. Talarmain L, Clarke MA, Shorthouse D, Cabrera-Cosme L, Kent DG, Fisher J, et al. HOXA9 has the hallmarks of a biological switch with implications in blood cancers. Nat Commun 2022; 13(1): 5829. [CrossRef] google scholar