miR‑186‑5p regulates the inflammatory response of chronic obstructive pulmonary disorder by targeting HIF‑1α

Fu,Yihui; Zhao,Jie; Chen,Jie; Zheng,Yamei; Mo,Rubing; Zhang,Lei; Zhang,Bingli; Lin,Qi; He,Chanyi; Li,Siguang; Lin,Lingsang; Xie,Tian; Ding,Yipeng

doi:10.3892/mmr.2024.13158

miR‑186‑5p regulates the inflammatory response of chronic obstructive pulmonary disorder by targeting HIF‑1α

Authors:
- Yihui Fu
- Jie Zhao
- Jie Chen
- Yamei Zheng
- Rubing Mo
- Lei Zhang
- Bingli Zhang
- Qi Lin
- Chanyi He
- Siguang Li
- Lingsang Lin
- Tian Xie
- Yipeng Ding
View Affiliations

Affiliations: Department of Pulmonary and Critical Care Medicine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570311, P.R. China, Department of General Practice, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570311, P.R. China
Published online on: January 8, 2024 https://doi.org/10.3892/mmr.2024.13158
Article Number: 34
Copyright: © Fu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Chronic obstructive pulmonary disorder (COPD) is a chronic respiratory disease that is a major cause of morbidity and mortality worldwide. Previous studies have shown that miR‑186‑5p expression is significantly increased in COPD and is involved in multiple physiological and pathological processes. However, the role of miRNA‑186‑5p in the inflammatory response of COPD remains unclear. In this study, an in vitro model of COPD was established using lipopolysaccharide (LPS)‑induced human bronchial epithelial cells (BEAS‑2B). CCK‑8 assays, flow cytometry, and a Muse cell analyzer were used to determine cell viability, cell cycle distribution, and apoptosis, respectively. The production of TNF‑α and IL‑6 were measured by ELISA. Reverse‑transcription‑quantitative PCR and western blotting were used to analyze mRNA and protein expression levels. The targeting relation between miR‑186‑5p and HIF‑1α was discovered using dual‑luciferase reporter assays. The results showed that transfection of miR‑186‑5p inhibitor inhibited cell proliferation and promoted cell apoptosis in the LPS‑induced BEAS‑2B cells. Inhibition of miR‑186‑5p markedly increased the levels of TNF‑α and IL‑6. miR‑186‑5p directly targeted and negatively regulated HIF‑1α expression. In addition, inhibition of miR‑186‑5p increased the expression of the NF‑κB pathway protein p‑p65. In conclusion, it was found that inhibiting miR‑186‑5p may improve inflammation of COPD through HIF‑1α in LPS‑induced BEAS‑2B cells, possibly by regulating NF‑κB signaling. These findings provide a novel potential avenue for the clinical management of COPD. Future research is required to determine the mechanism of the interaction between miR‑186‑5p and HIF‑1α in COPD.

View Figures

View References

1	Christenson SA, Smith BM, Bafadhel M and Putcha N: Chronic obstructive pulmonary disease. Lancet. 399:2227–2242. 2022. View Article : Google Scholar : PubMed/NCBI
2	Celli B, Fabbri L, Criner G, Martinez FJ, Mannino D, Vogelmeier C, Montes de Oca M, Papi A, Sin DD, Han MK and Agusti A: Definition and nomenclature of chronic obstructive pulmonary disease: Time for its revision. Am J Respir Crit Care Med. 206:1317–1325. 2022. View Article : Google Scholar : PubMed/NCBI
3	Safiri S, Carson-Chahhoud K, Noori M, Nejadghaderi SA, Sullman MJM, Ahmadian Heris J, Ansarin K, Mansournia MA, Collins GS, Kolahi AA and Kaufman JS: Burden of chronic obstructive pulmonary disease and its attributable risk factors in 204 countries and territories, 1990–2019: results from the Global Burden of Disease Study 2019. BMJ. 378:e0696792022. View Article : Google Scholar : PubMed/NCBI
4	Silverman EK: Genetics of COPD. Annu Rev Physiol. 82:413–431. 2020. View Article : Google Scholar : PubMed/NCBI
5	Zhang PD, Zhang XR, Zhang A, Li ZH, Liu D, Zhang YJ and Mao C: Associations of genetic risk and smoking with incident COPD. Eur Respir J. 59:21013202022. View Article : Google Scholar : PubMed/NCBI
6	Adeloye D, Song P, Zhu Y, Campbell H, Sheikh A and Rudan I: Global, regional, and national prevalence of, and risk factors for, chronic obstructive pulmonary disease (COPD) in 2019: A systematic review and modelling analysis. Lancet Respir Med. 10:447–458. 2022. View Article : Google Scholar : PubMed/NCBI
7	Yin P, Wu J, Wang L, Luo C, Ouyang L, Tang X, Liu J, Liu Y, Qi J, Zhou M and Lai T: The Burden of COPD in China and Its Provinces: Findings From the Global Burden of Disease Study 2019. Front Public Health. 10:8594992022. View Article : Google Scholar : PubMed/NCBI
8	Barnes PJ: Inflammatory mechanisms in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 138:16–27. 2016. View Article : Google Scholar : PubMed/NCBI
9	Ghanbarian H, Yıldız MT and Tutar Y: MicroRNA Targeting. Methods Mol Biol. 2257:105–130. 2022. View Article : Google Scholar : PubMed/NCBI
10	Vishnoi A and Rani S: miRNA Biogenesis and Regulation of Diseases: An Updated Overview. Methods Mol Biol. 2595:1–12. 2023. View Article : Google Scholar : PubMed/NCBI
11	Specjalski K and Jassem E: MicroRNAs: Potential Biomarkers and Targets of Therapy in Allergic Diseases? Arch Immunol Ther Exp (Warsz). 67:213–223. 2019. View Article : Google Scholar : PubMed/NCBI
12	Liang Q, He J, Yang Q, Zhang Q and Xu Y: MicroRNA-335-5p alleviates inflammatory response, airway fibrosis, and autophagy in childhood asthma through targeted regulation of autophagy related 5. Bioengineered. 13:1791–1801. 2022. View Article : Google Scholar : PubMed/NCBI
13	Li X, Gong Y, Lin X, Lin Q, Luo J, Yu T, Xu J, Chen L, Xu L and Hu Y: Down-regulation of microRNA-155 suppressed Candida albicans induced acute lung injury by activating SOCS1 and inhibiting inflammation response. J Microbiol. 60:402–410. 2022. View Article : Google Scholar : PubMed/NCBI
14	Huang X, Zhu Z, Guo X and Kong X: The roles of microRNAs in the pathogenesis of chronic obstructive pulmonary disease. Int Immunopharmacol. 67:335–347. 2019. View Article : Google Scholar : PubMed/NCBI
15	Roffel MP, Bracke KR, Heijink IH and Maes T: miR-223: A key regulator in the innate immune response in asthma and COPD. Front Med (Lausanne). 7:1962020. View Article : Google Scholar : PubMed/NCBI
16	Zhang J, Xu Z, Kong L, Gao H, Zhang Y, Zheng Y and Wan 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. 15:2991–3001. 2020. View Article : Google Scholar : PubMed/NCBI
17	Kim RY, Sunkara KP, Bracke KR, Jarnicki AG, Donovan C, Hsu AC, Ieni A, Beckett EL, Galvão I, Wijnant S, et al: A microRNA-21-mediated SATB1/S100A9/NF-κB axis promotes chronic obstructive pulmonary disease pathogenesis. Sci Transl Med. 13:eaav72232021. View Article : Google Scholar : PubMed/NCBI
18	Ding Y, Tian Z, Yang H, Yao H, He P, Ouyang Y, Yao J, Li M and Jin T: MicroRNA expression profiles of whole blood in chronic obstructive pulmonary disease. Int J Clin Experiment Pathol. 10:4860–4865. 2017.
19	Cai SC, Li XP, Li X, Tang GY, Yi LM and Hu XS: Oleanolic Acid Inhibits Neuronal Pyroptosis in Ischaemic Stroke by Inhibiting miR-186-5p Expression. Exp Neurobiol. 30:401–414. 2021. View Article : Google Scholar : PubMed/NCBI
20	Yang P, Liang K, Wang W, Zhou D, Chen Y, Jiang X, Fu R, Zhu B and Lin X: LncRNA SOX2-OTinhibitionprotects against myocardialischemia/reperfusion-inducedinjury via themicroRNA-186-5p (miR-186-5p)/Yin Yang 1 (YY1) pathway. Bioengineered. 13:280–290. 2022. View Article : Google Scholar : PubMed/NCBI
21	Nie Y and Wang F: Inhibiting miR-186-5p relieves traumatic brain injury by regulating insulin-like growth factor-I-NLRP3/ASC/caspase-1 signaling pathway. Neuroreport. 34:156–164. 2023. View Article : Google Scholar : PubMed/NCBI
22	Li R, Xu F, Wu X, Ji S and Xia R: CUL1-Mediated organelle fission pathway inhibits the development of chronic obstructive pulmonary disease. Comput Math Methods Med. 2020:53901072020. View Article : Google Scholar : PubMed/NCBI
23	Rong B, Liu Y, Li M, Fu T, Gao W and Liu H: Correlation of serum levels of HIF-1α and IL-19 with the disease progression of COPD: A retrospective study. Int J Chron Obstruct Pulmon Dis. 13:3791–3803. 2018. View Article : Google Scholar : PubMed/NCBI
24	Fu X and Zhang F: Role of the HIF-1 signaling pathway in chronic obstructive pulmonary disease. Exp Ther Med. 16:4553–4561. 2018.PubMed/NCBI
25	Alharbi KS, Fuloria NK, Fuloria S, Rahman SB, Al-Malki WH, Javed Shaikh MA, Thangavelu L, Singh SK, Rama Raju Allam VS, Jha NK, et al: Nuclear factor-kappa B and its role in inflammatory lung disease. Chem Biol Interact. 345:1095682021. View Article : Google Scholar : PubMed/NCBI
26	Tan H and Zhao L: lncRNA nuclear-enriched abundant transcript 1 promotes cell proliferation and invasion by targeting miR-186-5p/HIF-1α in osteosarcoma. J Cell Biochem. 120:6502–6514. 2019. View Article : Google Scholar : PubMed/NCBI
27	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
28	Wang Z, Sha HH and Li HJ: Functions and mechanisms of miR-186 in human cancer. Biomed Pharmacother. 119:1094282019. View Article : Google Scholar : PubMed/NCBI
29	Becker V, Yuan X, Boewe AS, Ampofo E, Ebert E, Hohneck J, Bohle RM, Meese E, Zhao Y, Menger MD, et al: Hypoxia-induced downregulation of microRNA-186-5p in endothelial cells promotes non-small cell lung cancer angiogenesis by upregulating protein kinase C alpha. Molecular therapy. Mol Ther Nucleic Acids. 31:421–436. 2023. View Article : Google Scholar : PubMed/NCBI
30	Lin L, Sun J, Wu D, Lin D, Sun D, Li Q, Chen J, Niu H, He P and Ding Y: MicroRNA-186 is associated with hypoxia-inducible factor-1α expression in chronic obstructive pulmonary disease. Mol Genet Genomic Med. 7:e5312019. View Article : Google Scholar : PubMed/NCBI
31	De la Garza MM, Cumpian AM, Daliri S, Castro-Pando S, Umer M, Gong L, Khosravi N, Caetano MS, Ramos-Castañeda M, Flores AG, et al: COPD-Type lung inflammation promotes K-ras mutant lung cancer through epithelial HIF-1α mediated tumor angiogenesis and proliferation. Oncotarget. 9:32972–32983. 2018. View Article : Google Scholar : PubMed/NCBI
32	Zhang HX, Yang JJ, Zhang SA, Zhang SM, Wang JX, Xu ZY and Lin RY: HIF-1α promotes inflammatory response of chronic obstructive pulmonary disease by activating EGFR/PI3K/AKT pathway. Eur Rev Med Pharmacol Sci. 22:6077–6084. 2018.PubMed/NCBI
33	Xu YR, Wang AL and Li YQ: Hypoxia-inducible factor 1-alpha is a driving mechanism linking chronic obstructive pulmonary disease to lung cancer. Front Oncol. 12:9845252022. View Article : Google Scholar : PubMed/NCBI
34	Jiang H, Zhu Y, Xu H, Sun Y and Li Q: Activation of hypoxia-inducible factor-1α via nuclear factor-κB in rats with chronic obstructive pulmonary disease. Acta Biochim Biophys Sin (Shanghai). 42:483–488. 2010. View Article : Google Scholar : PubMed/NCBI
35	Schuliga M: NF-kappaB signaling in chronic inflammatory airway disease. Biomolecules. 5:1266–1283. 2015. View Article : Google Scholar : PubMed/NCBI