Bioinformatic analysis of circular RNAs differential expression in myelodysplastic syndrome_West China Medical Journal

Authors：

LIU Yifan ¹ ,  XI Yaming ²

1. The First School of Clinical Medicine, Lanzhou University, Lanzhou, Gansu 730000, P. R. China;
2. Department of Hematology, the First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P. R. China;

Corresponding author：

XI Yaming, Email: xiyaming02@163.com

Keywords：

Bioinformatics; myelodysplastic syndrome; circular RNA; competing endogenous RNA

DOI：

10.7507/1002-0179.202303031

Video：

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Objective To explore the mode and role of differential expression of circular RNAs (circRNAs) in myelodysplastic syndrome (MDS). Methods We preprocessed and analyzed the circRNA expression profile datasets GSE163386, GSE94591, and GSE81173 in the GEO (Gene Expression Omnibus) database. By using the circBank database and the ENCORI, miRDB, and miRWalk databases to predict microRNAs (miRNAs) that interacted with differentially expressed circRNAs and messenger RNAs (mRNAs), the circRNA-miRNA-mRNA axis was constructed. We retrieved miRNAs related to MDS in PubMed and further obtained competing endogenous RNA (ceRNA) networks related to MDS by taking intersections. Results Through analysis, 128 differentially expressed circRNAs were identified, 48 highly expressed, and 80 low expressed. Among differentially expressed circRNAs with multiple differences>10, 3 were upregulated and 11 were downregulated. Through analysis, 101 differentially expressed mRNA were identified, with 9 upregulated and 92 downregulated. Intersecting with the MDS related miRNAs retrieved by PubMed, we further obtained the MDS related ceRNA network, namely circRNA (has_circ_0061137)-miRNA (has-miR-16-5p)-mRNA (RUBCNL, TBC1D9, SLC16A6) and circRNA (has_circ_0061137)-miRNA (has-miR-125b-5p)-mRNA (CCR5, SLC16A6, IRF4), all of which were downregulated. Conclusion The ceRNA networks revealed in this study may help elucidate the circRNA mechanism in MDS.

Citation： LIU Yifan, XI Yaming. Bioinformatic analysis of circular RNAs differential expression in myelodysplastic syndrome. West China Medical Journal, 2023, 38(7): 1053-1057. doi: 10.7507/1002-0179.202303031 Copy

1.	Frumm SM, Shimony S, Stone RM, et al. Why do we not have more drugs approved for MDS? A critical viewpoint on novel drug development in MDS. Blood Rev, 2023, 60: 101056.
2.	Otto G. Myelodysplastic syndromes. Nat Rev Dis Primers, 2022, 8(1): 73.
3.	Chen LL. The biogenesis and emerging roles of circular RNAs. Nat Rev Mol Cell Biol, 2016, 17(4): 205-211.
4.	Liu CX, Chen LL. Circular RNAs: characterization, cellular roles, and applications. Cell, 2022, 185(12): 2016-2034.
5.	Misir S, Wu N, Yang BB. Specific expression and functions of circular RNAs. Cell Death Differ, 2022, 29(3): 481-491.
6.	Rahnama S, Bakhshinejad B, Farzam F, et al. Identification of dysregulated competing endogenous RNA networks in glioblastoma: a way toward improved therapeutic opportunities. Life Sci, 2021, 277: 119488.
7.	Salmena L, Poliseno L, Tay Y, et al. A ceRNA hypothesis: the rosetta stone of a hidden RNA language?. Cell, 2011, 146(3): 353-358.
8.	Li W, Zhong C, Jiao J, et al. Characterization of hsa_circ_0004277 as a new biomarker for acute myeloid leukemia via circular RNA profile and bioinformatics analysis. Int J Mol Sci, 2017, 18(3): 597.
9.	Li X, Yang L, Chen LL. The biogenesis, functions, and challenges of circular RNAs. Mol Cell, 2018, 71(3): 428-442.
10.	Jeck WR, Sharpless NE. Detecting and characterizing circular RNAs. Nat Biotechnol, 2014, 32(5): 453-461.
11.	Liu Z, Wang T, She Y, et al. N⁶-methyladenosine-modified circIGF2BP3 inhibits CD8⁺ T-cell responses to facilitate tumor immune evasion by promoting the deubiquitination of PD-L1 in non-small cell lung cancer. Mol Cancer, 2021, 20(1): 105.
12.	Yang C, Wu S, Mou Z, et al. Exosome-derived circTRPS1 promotes malignant phenotype and CD8⁺ T cell exhaustion in bladder cancer microenvironments. Mol Ther, 2022, 30(3): 1054-1070.
13.	Zhang Y, Jiang J, Zhang J, et al. CircDIDO1 inhibits gastric cancer progression by encoding a novel DIDO1-529aa protein and regulating PRDX2 protein stability. Mol Cancer, 2021, 20(1): 101.
14.	Zhang L, Tao H, Li J, et al. Comprehensive analysis of the competing endogenous circRNA-lncRNA-miRNA-mRNA network and identification of a novel potential biomarker for hepatocellular carcinoma. Aging (Albany NY), 2021, 13(12): 15990-16008.
15.	Špringer T, Krejčík Z, Homola J. Detecting attomolar concentrations of microRNA related to myelodysplastic syndromes in blood plasma using a novel sandwich assay with nanoparticle release. Biosens Bioelectron, 2021, 194: 113613.
16.	Zeng Z, Xia L, Fan S, et al. Circular RNA circMAP3K5 acts as a microRNA-22-3p sponge to promote resolution of intimal hyperplasia via TET2-mediated smooth muscle cell differentiation. Circulation, 2021, 143(4): 354-371.
17.	Cheng X, Sun Q. RUBCNL/pacer and RUBCN/rubicon in regulation of autolysosome formation and lipid metabolism. Autophagy, 2019, 15(6): 1120-1121.
18.	Nozawa T, Sano S, Minowa-Nozawa A, et al. TBC1D9 regulates TBK1 activation through Ca2⁺ signaling in selective autophagy. Nat Commun, 2020, 11(1): 770.
19.	Mortensen M, Soilleux EJ, Djordjevic G, et al. The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance. J Exp Med, 2011, 208(3): 455-467.
20.	Dai W, Liu H, Chen K, et al. Genetic variants in PDSS1 and SLC16A6 of the ketone body metabolic pathway predict cutaneous melanoma-specific survival. Mol Carcinog, 2020, 59(6): 640-650.
21.	丁宇斌, 唐旭东. 骨髓增生异常综合征进展过程中核心基因的生物信息学分析. 临床与实验病理学杂志, 2022, 38(3): 344-347.
22.	González-Arriagada WA, García IE, Martínez-Flores R, et al. Therapeutic perspectives of HIV-associated chemokine receptor (CCR5 and CXCR4) antagonists in carcinomas. Int J Mol Sci, 2022, 24(1): 478.
23.	Zilio S, Bicciato S, Weed D, et al. CCR1 and CCR5 mediate cancer-induced myelopoiesis and differentiation of myeloid cells in the tumor. J Immunother Cancer, 2022, 10(1): e003131.

1. Frumm SM, Shimony S, Stone RM, et al. Why do we not have more drugs approved for MDS? A critical viewpoint on novel drug development in MDS. Blood Rev, 2023, 60: 101056.
2. Otto G. Myelodysplastic syndromes. Nat Rev Dis Primers, 2022, 8(1): 73.
3. Chen LL. The biogenesis and emerging roles of circular RNAs. Nat Rev Mol Cell Biol, 2016, 17(4): 205-211.
4. Liu CX, Chen LL. Circular RNAs: characterization, cellular roles, and applications. Cell, 2022, 185(12): 2016-2034.
5. Misir S, Wu N, Yang BB. Specific expression and functions of circular RNAs. Cell Death Differ, 2022, 29(3): 481-491.
6. Rahnama S, Bakhshinejad B, Farzam F, et al. Identification of dysregulated competing endogenous RNA networks in glioblastoma: a way toward improved therapeutic opportunities. Life Sci, 2021, 277: 119488.
7. Salmena L, Poliseno L, Tay Y, et al. A ceRNA hypothesis: the rosetta stone of a hidden RNA language?. Cell, 2011, 146(3): 353-358.
8. Li W, Zhong C, Jiao J, et al. Characterization of hsa_circ_0004277 as a new biomarker for acute myeloid leukemia via circular RNA profile and bioinformatics analysis. Int J Mol Sci, 2017, 18(3): 597.
9. Li X, Yang L, Chen LL. The biogenesis, functions, and challenges of circular RNAs. Mol Cell, 2018, 71(3): 428-442.
10. Jeck WR, Sharpless NE. Detecting and characterizing circular RNAs. Nat Biotechnol, 2014, 32(5): 453-461.
11. Liu Z, Wang T, She Y, et al. N⁶-methyladenosine-modified circIGF2BP3 inhibits CD8⁺ T-cell responses to facilitate tumor immune evasion by promoting the deubiquitination of PD-L1 in non-small cell lung cancer. Mol Cancer, 2021, 20(1): 105.
12. Yang C, Wu S, Mou Z, et al. Exosome-derived circTRPS1 promotes malignant phenotype and CD8⁺ T cell exhaustion in bladder cancer microenvironments. Mol Ther, 2022, 30(3): 1054-1070.
13. Zhang Y, Jiang J, Zhang J, et al. CircDIDO1 inhibits gastric cancer progression by encoding a novel DIDO1-529aa protein and regulating PRDX2 protein stability. Mol Cancer, 2021, 20(1): 101.
14. Zhang L, Tao H, Li J, et al. Comprehensive analysis of the competing endogenous circRNA-lncRNA-miRNA-mRNA network and identification of a novel potential biomarker for hepatocellular carcinoma. Aging (Albany NY), 2021, 13(12): 15990-16008.
15. Špringer T, Krejčík Z, Homola J. Detecting attomolar concentrations of microRNA related to myelodysplastic syndromes in blood plasma using a novel sandwich assay with nanoparticle release. Biosens Bioelectron, 2021, 194: 113613.
16. Zeng Z, Xia L, Fan S, et al. Circular RNA circMAP3K5 acts as a microRNA-22-3p sponge to promote resolution of intimal hyperplasia via TET2-mediated smooth muscle cell differentiation. Circulation, 2021, 143(4): 354-371.
17. Cheng X, Sun Q. RUBCNL/pacer and RUBCN/rubicon in regulation of autolysosome formation and lipid metabolism. Autophagy, 2019, 15(6): 1120-1121.
18. Nozawa T, Sano S, Minowa-Nozawa A, et al. TBC1D9 regulates TBK1 activation through Ca2⁺ signaling in selective autophagy. Nat Commun, 2020, 11(1): 770.
19. Mortensen M, Soilleux EJ, Djordjevic G, et al. The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance. J Exp Med, 2011, 208(3): 455-467.
20. Dai W, Liu H, Chen K, et al. Genetic variants in PDSS1 and SLC16A6 of the ketone body metabolic pathway predict cutaneous melanoma-specific survival. Mol Carcinog, 2020, 59(6): 640-650.
21. 丁宇斌, 唐旭东. 骨髓增生异常综合征进展过程中核心基因的生物信息学分析. 临床与实验病理学杂志, 2022, 38(3): 344-347.
22. González-Arriagada WA, García IE, Martínez-Flores R, et al. Therapeutic perspectives of HIV-associated chemokine receptor (CCR5 and CXCR4) antagonists in carcinomas. Int J Mol Sci, 2022, 24(1): 478.
23. Zilio S, Bicciato S, Weed D, et al. CCR1 and CCR5 mediate cancer-induced myelopoiesis and differentiation of myeloid cells in the tumor. J Immunother Cancer, 2022, 10(1): e003131.

West China Medical Journal

Bioinformatic analysis of circular RNAs differential expression in myelodysplastic syndrome

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