Screening and bioinformatics analysis of differential microRNA in nitroglycerin-tolerant rat aorta

doi:10.12092/j.issn.1009-2501.2018.10.001

Abstract

Abstract:

AIM: To screen the differential expression of microRNA (miRNA) in nitroglycerin-tolerant rat aorta and to analyze their target genes and function. METHODS: Sprague Dawley (SD) rats were treated with nitroglycerin (100 mg·kg^-1·time^-1 for 3 days, three times a day, s.c). Then, miRNA sequencing technology and qRT-PCR were used to find differential miRNAs involved in nitroglycerin-tolerant rats. Furthermore, bioinformatics analysis was performed to predict target genes regulated by these differential miRNAs, and to analyze the enriched gene ontology (GO) and signaling pathway. RESULTS: Compared with control group, the expression of 28 miRNAs changed significantly in nitroglycerin-tolerant group, of which 16 were known. 12 up-regulated and 4 down-regulated were obtained among the 16 miRNAs. The expression of miR-487b-3p and miR-503-5p were detected by qRT-PCR showed the similar trend as well as the sequencing results. Bioinformatics analysis showed that the target genes of differential miRNAs were mainly enriched in protein binding and metabolic pathways. CONCLUSION: The expression of miRNA in nitroglycerin-tolerant rat aorta changes significantly, and these differential miRNAs are involved in the development of nitroglycerin tolerance by regulating their target genes.

Key words: nitroglycerin, tolerance, microRNA, bioinformatics

CLC Number:

R965.2

ZENG Zhenhua, LIU Jianxin, CAO Chunya, WU Weihua. Screening and bioinformatics analysis of differential microRNA in nitroglycerin-tolerant rat aorta[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(10): 1081-1087.

References

［1］窦豆, 高远生. 硝酸甘油耐受机制的研究进展［J］. 生理科学进展, 2009, 40(4): 321-324.
［2］Munzel T, Daiber A, Gori T. More answers to the still unresolved question of nitrate tolerance［J］. Eur Heart J, 2013, 34(34): 2666-2673.
［3］Daiber A, Munzel T. Organic nitrate therapy, nitrate tolerance, and nitrate-induced endothelial dysfunction: emphasis on redox biology and oxidative stress［J］. Antioxid Redox Signal, 2015, 23(11): 899-942.
［4］Barwari T, Joshi A, Mayr M. MicroRNAs in cardiovascular disease［J］. J Am Coll Cardiol, 2016, 68(23): 2577-2584.
［5］Bai YP, Zhang JX, Sun Q, et al. Induction of microRNA-199 by nitric oxide in endothelial cells is required for nitrovasodilator resistance via targeting of prostaglandin I2 synthase［J］. Circulation, 2018. https://doi.org/10.1161/CIRCULATIONAHA.117.029206.
［6］Mens MMJ, Ghanbari M. Cell cycle regulation of stem cells by microRNAs［J］. Stem Cell Rev, 2018, 14(3): 309-322.
［7］吴卫华,胡长平. MicroRNA-21在心血管疾病中的作用［J］. 中国临床药理学与治疗学, 2012, 17(6): 709-714.
［8］Hagiwara S, Kantharidis P, Cooper ME. MicroRNA as biomarkers and regulator of cardiovascular development and disease［J］. Curr Pharm Des, 2014, 20(14): 2347-2370.
［9］Leach JP, Martin JF. Cardiomyocyte proliferation for therapeutic regeneration［J］. Curr Cardiol Rep, 2018, 20(8): 63.
［10］Li MP, Hu YD, Hu XL, et al. MiRNAs and miRNA polymorphisms modify drug response［J］. Int J Environ Res Public Health, 2016, 13(11): 1096.
［11］Mihanfar A, Fattahi A, Nejabati HR. MicroRNA-mediated drug resistance in ovarian cancer［J］. J Cell Physiol, 2017, 1-12.
［12］Kim J, Kang Y, Kojima Y, et al. An endothelial apelin-FGF link mediated by miR-424 and miR-503 is disrupted in pulmonary arterial hypertension［J］. Nat Med, 2013, 19(1): 74-82.
［13］Zhu JJ, Liu YF, Zhang YP, et al. VAMP3 and SNAP23 mediate the disturbed flow-induced endothelial microRNA secretion and smooth muscle hyperplasia［J］. Proc Natl Acad Sci USA, 2017, 114(31): 8271-8276.
［14］Feng N, Wang Z, Zhang Z, et al. miR-487b promotes human umbilical vein endothelial cell proliferation, migration, invasion and tube formation through regulating THBS1［J］. Neurosci Lett, 2015, 30(591): 1-7.
［15］Nossent AY, Eskildsen TV, Andersen LB, et al. The 14q32 microRNA-487b targets the antiapoptotic insulin receptor substrate 1 in hypertension-induced remodeling of the aorta［J］. Ann Surg, 2013, 258(5): 743-751.
［16］Welten SM, Bastiaansen AJ, de Jong RC, et al. Inhibition of 14q32 MicroRNAs miR-329, miR-487b, miR-494, and miR-495 increases neovascularization and blood flow recovery after ischemia［J］. Circ Res, 2014, 115(8): 696-708.
［17］Kriegel AJ, Liu Y, Fang Y, et al. The miR-29 family: genomics, cell biology, and relevance to renal and cardiovascular injury［J］. Physiol Genomics, 2012, 44(4): 237-44.
［18］Widlansky ME, Jensen DM, Wang J, et al. miR-29 contributes to normal endothelial function and can restore it in cardiometabolic disorders［J］. EMBO Mol Med, 2018: e8046.
［19］Chen M, Ma G, Yue Y, et al. Downregulation of the miR-30 family microRNAs contributes to endoplasmic reticulum stress in cardiac muscle and vascular smooth muscle cells［J］. Int J Cardiol, 2014, 173(1): 65-73.
［20］Foulquier S, Daskalopoulos EP, Lluri G, et al. WNT signaling in cardiac and vascular disease［J］. Pharmacol Rev, 2018, 70(1): 68-141.
［21］Zihni C, Mills C, Matter K, et al. Tight junctions: from simple barriers to multifunctional molecular gates［J］. Nat Rev Mol Cell Biol, 2016, 17(9): 564-580.

[1]	LI Shixu, LI Linyun, WANG Xin, LI Ke, BIAN Hua. Effects of Ginkgo biloba extract on renal injury in rats with experimental renal failure through miR-145/FOXO1 axis [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(7): 728-735.
[2]	PENG Fusheng, HUANG Xiaohui, LI Peng, TANG Jian'er. miR-34a inhibits proliferation of prostate cancer LNCaP cells by regulating androgen receptor gene [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2021, 26(1): 10-17.
[3]	XU Lina, LI Yue, PENG Jinyong. microRNA and drug-induced liver injury [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(7): 803-809.
[4]	LI Guinv, REN Shaolin, SHEN Ruiming, JI Yongneng, CAI Cairong, SU Ruo. Metformin combined with glucocorticoid in the treatment of SLE patients with IGT [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(6): 670-676.
[5]	JIANG Bingbing. Research progress on microRNAs in Huntington's disease [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(6): 677-685.
[6]	LIU Jianhui, ZHOU Genhong, LI Chunlin, BAO Meihua, LIU Fangyi. Identification of myelodysplastic syndromes related long noncoding RNA by bioinformatics [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(12): 1351-1356.
[7]	LIU Yujia, LI Li, HU Xiaoping, ZHONG Like, LI Jingjing, HUANG Ping, ZHANG Yiwen. A correlation analysis between survival rate and the characteristic gene of gastric cancer based on bioinformatics [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(8): 852-859.
[8]	SHEN Lei, WANG Keke, YANG Jingke, ZHAO Juntao, MENG Xiangguang, YUAN Yiqiang. Advances in drugs and genetic pharmacology for heart failure [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(3): 343-349.
[9]	ZHU Linjia, YUAN Shaofei, SHANGGUAN Zongxiao, CI Xiao, ZHAO Renguo, LI Yuping. Ultrasound-microbubbles mediated microRNA-449a inhibits lung cancer cell growth via the regulation of Notch1 [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(12): 1385-1393.
[10]	SONG Houpan, ZENG Meiyan, CHEN Xiaojuan, CHEN Xinyi, PENG Jun, ZHOU Yasha, YANG Yijing, YANG Tao, CAI Xiong, PENG Qinghua. Molecular network regulation mechanism of Lycii Fructus in promoting directional differentiation of iris pigment epithelial cells to treat retinitis pigmentosa [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(12): 1402-1414.
[11]	HAN Chenyang, YANG Yi, LI Wenyang, WANG Jin, GUO Li. Inhibitory effect of MicroRNA-136 targeting CD163 on the polarization of CD68+CD163+M2 macrophages [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(1): 1-8.
[12]	SHEN Binbin, ZHOU Jun, LI Liang, LU Ning, YAO Ming. Long non-coding RNA TSIX regulates the proliferation of human pancreatic cancer cells by targeting miR-384 [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(6): 621-626.
[13]	LIU lei, LI Yixiao, WAN Bo, ZENG Qing. miR-200c induces resistance to doxorubicin through the Wnt/beta-catenin signaling pathway in bladder cancer cells [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(5): 510-516.
[14]	XU Ming, CUI Peng, YE Min, NI Xiong, WANG Tingfeng, MIN Zhijun. Insights into tumor suppression mechanism of miRNA-101 in medullary thyroid carcinoma [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(5): 524-530.
[15]	ZHANG Yiwen, LOU Qianwen, ZHONG Like, PAN Zongfu, FANG Luo, HUANG Ping. Study on the differences gene between proximal and distal colon cancer based on GEO database by bioinformatics [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(4): 422-427.