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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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Research Article

Differential miRNA Profiling Reveals miR-4433a-5p as a Key Regulator of Chronic Obstructive Pulmonary Disease Progression via PIK3R2- mediated Phenotypic Modulation

Author(s): Siming Tao, Chunyan Liao, Yide Wang, Dan Xu, Zheng Li and Fengsen Li*

Volume 27, Issue 16, 2024

Published on: 04 January, 2024

Page: [2323 - 2334] Pages: 12

DOI: 10.2174/0113862073243966231030093213

Price: $65

Abstract

Objective: In this study, a high-throughput sequencing technology was used to screen the differentially expressed miRNA in the patients with "fast" and "slow" progression of chronic obstructive pulmonary disease (COPD). Moreover, the possible mechanism affecting the progression of COPD was preliminarily analyzed based on the target genes of candidate miRNAs.

Methods: The "fast" progressive COPD group included 6 cases, "slow" and Normal progressive COPD groups included 5 cases each, and COPD group included 3 cases. The peripheral blood samples were taken from the participants, followed by total RNA extraction and high throughput miRNA sequencing. The differentially expressed miRNAs among the progressive COPD groups were identified using bioinformatics analysis. Then, the candidate miRNAs were externally verified. In addition, the target gene of this miRNA was identified, and its effects on cell activity, cell cycle, apoptosis, and other biological phenotypes of COPD were analyzed.

Results: Compared to the Normal group, a total of 35, 16, and 7 differentially expressed miRNAs were identified in the "fast" progressive COPD, "slow" progressive COPD group, and COPD group, respectively. The results were further confirmed using dual-luciferase reporter assay and transfection tests with phosphoinositide- 3-kinase, regulatory subunit 2 (PIK3R2) as a target gene of miR-4433a-5p; the result showed a negative regulatory correlation between the miRNA and its target gene. The phenotype detection showed that the activation of the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway might participate in the progression of COPD by promoting the proliferation of inflammatory A549 cells and inhibiting cellular apoptosis.

Conclusions: MiR-4433a-5p can be used as a marker and potential therapeutic target for the progression of COPD. As a target gene of miR-4433a-5p, PIK3R2 can affect the progression of COPD by regulating phenotypes, such as cellular proliferation and apoptosis.

« Previous Next »
[1]
Li, F.; Gao, Z.; Jing, J.; Xu, D. Application of the Delphi method in the criterion of “fast”, “slow” development of chronic obstructive pulmonary disease. Xinjiang Yike Daxue Xuebao, 2012, (10), 43-45.
[2]
Xu, Q.; Xu, D.; Li, F. Delphi analysis on development speed of chronic obstructive pulmonary disease. China Medical Herald., 2013, 10(6), 165-167.
[3]
Wang, M.; Huang, Y.; Liang, Z.; Liu, D.; Lu, Y.; Dai, Y.; Feng, G.; Wang, C. Plasma mi RNAS might be promising biomarkers of chronic obstructive pulmonary disease. Clin. Respir. J., 2016, 10(1), 104-111.
[http://dx.doi.org/10.1111/crj.12194] [PMID: 25102970]
[4]
Yamada, M. The Roles of MicroRNAs and Extracellular Vesicles in the Pathogeneses of Idiopathic Pulmonary Fibrosis and Acute Respiratory Distress Syndrome. Tohoku J. Exp. Med., 2020, 251(4), 313-326.
[http://dx.doi.org/10.1620/tjem.251.313] [PMID: 32779621]
[5]
Barreiro, E. The role of MicroRNAs in COPD muscle dysfunction and mass loss: Implications on the clinic. Expert Rev. Respir. Med., 2016, 10(9), 1011-1022.
[http://dx.doi.org/10.1080/17476348.2016.1206819] [PMID: 27348064]
[6]
Xing, X.; Hu, L.; Guo, Y.; Bloom, M.S.; Li, S.; Chen, G.; Yim, S.H.L.; Gurram, N.; Yang, M.; Xiao, X.; Xu, S.; Wei, Q.; Yu, H.; Yang, B.; Zeng, X.; Chen, W.; Hu, Q.; Dong, G. Interactions between ambient air pollution and obesity on lung function in children: The Seven Northeastern Chinese Cities (SNEC) Study. Sci. Total Environ., 2020, 699, 134397.
[http://dx.doi.org/10.1016/j.scitotenv.2019.134397] [PMID: 31677469]
[7]
Notarte, K.I.; Senanayake, S.; Macaranas, I.; Albano, P.M.; Mundo, L.; Fennell, E.; Leoncini, L.; Murray, P. MicroRNA and other non-coding RNAs in epstein–barr virus-associated cancers. Cancers (Basel), 2021, 13(15), 3909.
[http://dx.doi.org/10.3390/cancers13153909] [PMID: 34359809]
[8]
Wang, C.; Xu, J.; Yang, L.; Xu, Y.; Zhang, X.; Bai, C.; Kang, J.; Ran, P.; Shen, H.; Wen, F.; Huang, K.; Yao, W.; Sun, T.; Shan, G.; Yang, T.; Lin, Y.; Wu, S.; Zhu, J.; Wang, R.; Shi, Z.; Zhao, J.; Ye, X.; Song, Y.; Wang, Q.; Zhou, Y.; Ding, L.; Yang, T.; Chen, Y.; Guo, Y.; Xiao, F.; Lu, Y.; Peng, X.; Zhang, B.; Xiao, D.; Chen, C.S.; Wang, Z.; Zhang, H.; Bu, X.; Zhang, X.; An, L.; Zhang, S.; Cao, Z.; Zhan, Q.; Yang, Y.; Cao, B.; Dai, H.; Liang, L.; He, J. Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): A national cross-sectional study. Lancet, 2018, 391(10131), 1706-1717.
[http://dx.doi.org/10.1016/S0140-6736(18)30841-9] [PMID: 29650248]
[9]
Zou, R.; Cai, H. Progressive fibrotic interstitial lung disease: new concepts and new opportunities. Zhonghua Jie He He Hu Xi Za Zhi, 2021, 44(6), 559-561.
[PMID: 34102715]
[10]
Jiang, H.D.; Chen, B. Interstitial lung disease revisited Zhonghua Yi Xue Za Zhi, 2021, 101(20), 1453-1457.
[PMID: 34044517]
[11]
Cui, H.; Su, X. Advances in epigenetics. China Medical Herald., 2014, 11(19), 152.
[12]
Zong, D.D.; Ouyang, R.Y.; Chen, P. Epigenetic mechanisms in chronic obstructive pulmonary disease. Eur. Rev. Med. Pharmacol. Sci., 2015, 19(5), 844-856.
[PMID: 25807439]
[13]
Duru, S. Epigenetic and current treatment approaches in chronic obstructive pulmonary disease. Tuberk. Toraks, 2016, 64(1), 47-52.
[http://dx.doi.org/10.5578/tt.7882] [PMID: 27266285]
[14]
Wang, R.; Xu, J.; Liu, H.; Zhao, Z. Peripheral leukocyte microRNAs as novel biomarkers for COPD. Int. J. Chron. Obstruct. Pulmon. Dis., 2017, 12, 1101-1112.
[http://dx.doi.org/10.2147/COPD.S130416] [PMID: 28435243]
[15]
Liu, X.; Qu, J.; Xue, W.; He, L.; Wang, J.; Xi, X.; Liu, X.; Yin, Y.; Qu, Y. Bioinformatics-based identification of potential microRNA biomarkers in frequent and non-frequent exacerbators of COPD. Int. J. Chron. Obstruct. Pulmon. Dis., 2018, 13, 1217-1228.
[http://dx.doi.org/10.2147/COPD.S163459] [PMID: 29713155]
[16]
Osei, E.T.; Florez-Sampedro, L.; Tasena, H.; Faiz, A.; Noordhoek, J.A.; Timens, W.; Postma, D.S.; Hackett, T.L.; Heijink, I.H.; Brandsma, C.A. miR-146a-5p plays an essential role in the aberrant epithelial–fibroblast cross-talk in COPD. Eur. Respir. J., 2017, 49(5), 1602538.
[http://dx.doi.org/10.1183/13993003.02538-2016] [PMID: 28546273]
[17]
Ong, J.; Faiz, A.; Timens, W.; van den Berge, M.; Terpstra, M.M.; Kok, K.; van den Berg, A.; Kluiver, J.; Brandsma, C.A. Marked TGF-β-regulated miRNA expression changes in both COPD and control lung fibroblasts. Sci. Rep., 2019, 9(1), 18214.
[http://dx.doi.org/10.1038/s41598-019-54728-4] [PMID: 31796837]
[18]
He, H.; Wang, H.; Pei, F.; Jiang, M. MiR-543 regulates the development of chronic obstructive pulmonary disease by targeting interleukin-33. Clin. Lab., 2018, 64(7), 1199-1205.
[http://dx.doi.org/10.7754/Clin.Lab.2018.180205]
[19]
Lin, L.; Sun, J.; Wu, D.; Lin, D.; Sun, D.; Li, Q. MicroRNA-186 is associated with hypoxia-inducible factor-1α expression in chronic obstructive pulmonary disease. Mol. Genet. Genomic Med., 2019, 7(3), e531.
[http://dx.doi.org/10.1002/mgg3.531]
[20]
Long, Y.J.; Liu, X.P.; Chen, S.S.; Zong, D.D.; Chen, Y.; Chen, P. miR-34a is involved in CSE-induced apoptosis of human pulmonary microvascular endothelial cells by targeting Notch-1 receptor protein. Respir. Res., 2018, 19(1), 21.
[http://dx.doi.org/10.1186/s12931-018-0722-2] [PMID: 29373969]
[21]
Zhang, J.; Xu, Z.; Kong, L.; Gao, H.; Zhang, Y.; Zheng, Y. miRNA-486-5p promotes COPD progression by targeting HAT1 to regulate the TLR4-triggered inflammatory response of alveolar macrophages. Int. J. Chron. Obstruct. Pulmon. Dis., 2020, 15, 2991-3001.
[22]
Kim, J.; Kim, D.Y.; Heo, H.R.; Choi, S.S.; Hong, S.H.; Kim, W.J. Role of miRNA-181a-2-3p in cadmium-induced inflammatory responses of human bronchial epithelial cells. J. Thorac. Dis., 2019, 11(7), 3055-3069.
[http://dx.doi.org/10.21037/jtd.2019.07.55] [PMID: 31463135]
[23]
Jing, X.; Luan, Z.; Liu, B. miR-558 reduces the damage of HBE cells exposed to cigarette smoke extract by targeting TNFRSF1A and inactivating TAK1/MAPK/NF-κB pathway. Immunol. Invest., 2022, 51(4), 787-801.
[http://dx.doi.org/10.1080/08820139.2021.1874977] [PMID: 33459100]
[24]
Gu, W.; Yuan, Y.; Yang, H.; Wu, H.; Wang, L.; Tang, Z.; Li, Q. Role of miR-195 in cigarette smoke-induced chronic obstructive pulmonary disease. Int. Immunopharmacol., 2018, 55, 49-54.
[http://dx.doi.org/10.1016/j.intimp.2017.11.030] [PMID: 29223853]
[25]
Sun, Y.; An, N.; Li, J.; Xia, J.; Tian, Y.; Zhao, P.; Liu, X.; Huang, H.; Gao, J.; Zhang, X. miRNA‐206 regulates human pulmonary microvascular endothelial cell apoptosis via targeting in chronic obstructive pulmonary disease. J. Cell. Biochem., 2019, 120(4), 6223-6236.
[http://dx.doi.org/10.1002/jcb.27910] [PMID: 30335896]
[26]
Wang, D.; He, S.; Liu, B.; Liu, C. MiR-27-3p regulates TLR2/4-dependent mouse alveolar macrophage activation by targetting PPARγ. Clin. Sci. , 2018, 132(9), 943-958.
[http://dx.doi.org/10.1042/CS20180083] [PMID: 29572385]
[27]
Wu, H.; Miao, Y.; Shang, L.Q.; Chen, R.L.; Yang, S.M. MiR-31 aggravates inflammation and apoptosis in COPD rats via activating the NF-κB signaling pathway. Eur. Rev. Med. Pharmacol. Sci., 2020, 24(18), 9626-9632.
[PMID: 33015806]
[28]
Wu, X. Depletion of miR-380 mitigates human bronchial epithelial cells injury to improve chronic obstructive pulmonary disease through targeting CHRNA4. Mol. Cell. Probes, 2020, 49, 101492.
[http://dx.doi.org/10.1016/j.mcp.2019.101492] [PMID: 31821848]
[29]
Wu, Y.; Guan, S.; Ge, Y.; Yang, Y.; Cao, Y.; Zhou, J. Cigarette smoke promotes chronic obstructive pulmonary disease (COPD) through the miR-130a/Wnt1 axis. Toxicol. In Vitro, 2020, 65, 104770.
[http://dx.doi.org/10.1016/j.tiv.2020.104770] [PMID: 31935487]
[30]
Zhang, J.L.; Yang, C.Q.; Deng, F. MicroRNA-378 inhibits the development of smoking-induced COPD by targeting TNF-α. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(20), 9009-9016.
[PMID: 31696490]
[31]
Wang, X.; Zhang, Y. Based on PI3K/Akt signaling pathway, the effects of Wumei Pill containing serum on the proliferation, invasion, migration and apoptosis of pancreatic cancer cells were investigated. Chinese J. Experi. Tradi. Medi. Form., 2022, 28(06), 34-42.
[32]
Luo, Y.; Jiang, H. Effect of miR-124 on proliferation and apoptosis of human gastric cancer MGC803 Cells by regulating PI3K/Akt signaling pathway. Zhejiang. Clin. Med J., 2020, 22(10), 1407-1410.
[33]
Du, S.; Su, Z.; Fan, X. Effect of sufentanil on proliferation, apoptosis, migration and invasion of lung cancer A549 cells via PI3K/Akt signaling pathway. Chin. J. Lab. Dis., 2021, 25(3), 429-433.
[34]
Shi, X.; Zhao, Y.; Luo, W. Effect of miR-29a on proliferation, migration and invasion of oral squamous cell carcinoma cells. Chin. J. Clin. Pharmacol., 2021, 37(3), 270-274.

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