MicroRNA-383 promotes reactive oxygen species-induced autophagy via downregulating peroxiredoxin 3 in human glioma U87 cells

Xu,Zhou; Zeng,Xingruo; Li,Mingchang; Liao,Jianming; Chen,Qianxue

doi:10.3892/etm.2021.9870

May-2021 Volume 21 Issue 5

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May-2021 Volume 21 Issue 5

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Article Open Access

MicroRNA-383 promotes reactive oxygen species-induced autophagy via downregulating peroxiredoxin 3 in human glioma U87 cells

Authors:
- Zhou Xu
- Xingruo Zeng
- Mingchang Li
- Jianming Liao
- Qianxue Chen
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Affiliations: Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Nephrology and Rheumatology, The Central Hospital of Wuhan, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China

Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 439
|
Published online on: February 26, 2021

https://doi.org/10.3892/etm.2021.9870
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Abstract

Peroxiredoxin 3 (PRDX3) is an abundant and effective enzyme, which aids in the removal of H₂O₂ in the mitochondria, thereby inhibiting cell autophagy. PRDX3 is a target protein of microRNA (miRNA/miR)-383, the overexpression of which has been found to inhibit the growth of glioma cells. We hypothesized that miR-383 serves an antitumor role by inhibiting oxidative stress during tumor growth. In the current study, human glioma U87 cells were transfected with pre-/short hairpin (sh)-PRDX3 vectors and miR-383 mimics/inhibitors. Apoptosis and reactive oxygen species (ROS) production were detected using flow cytometry. Autophagy was examined using acridine orange staining, and the expression of cytoplasmic autophagy-related proteins [autophagy-related protein 9 (ATG9), Ras-related protein Rab-1A (Rab1) and p62] was determined using western blot analysis. The interaction between miR-383 and PRDX3 was assessed using a dual-luciferase assay. The results indicated that both sh-PRDX3 and miR-383 mimics promoted apoptosis and increased the level of mitochondrial ROS, whilst acridine orange staining revealed that sh-PRDX3 promoted autophagy in U87 cells compared with that in the control cells. The detection of autophagic proteins indicated that sh-PRDX3 and miR-383 mimics increased the protein expression level of ATG9 and RAB1, and inhibited that of p62. On the contrary, the effect of miR-383 mimics was opposite to that of pre-PRDX3 in U87 cells. Reverse transcription-quantitative PCR and western blot assays revealed that miR-383 was negatively associated with PRDX3 in U87 cells. miR-383 was indicated to interact with PRDX3, as demonstrated using a dual-luciferase assay. In conclusion, the present study demonstrated that miR-383 induced cell apoptosis and mitochondrial ROS production by downregulating PRDX3 in U87 cells, thereby promoting oxidative stress-induced autophagy.

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1	Lapointe S, Perry A and Butowski NA: Primary brain tumours in adults. Lancet. 392:432–446. 2018.PubMed/NCBI View Article : Google Scholar
2	Piccolo SR and Frey LJ: Clinical and molecular models of glioblastoma multiforme survival. Int J Data Min Bioinform. 7:245–265. 2013.PubMed/NCBI View Article : Google Scholar
3	Fasolo F, Di Gregoli K, Maegdefessel L and Johnson JL: Non-coding RNAs in cardiovascular cell biology and atherosclerosis. Cardiovasc Res. 115:1732–1756. 2019.PubMed/NCBI View Article : Google Scholar
4	Correia de Sousa M, Gjorgjieva M, Dolicka D, Sobolewski C and Foti M: Deciphering miRNAs' action through miRNA editing. Int J Mol Sci. 20(6249)2019.PubMed/NCBI View Article : Google Scholar
5	Wang F, Liu W, Jin Y, Wang F and Ma J: Prenatal and neonatal exposure to perfluorooctane sulfonic acid results in aberrant changes in miRNA expression profile and levels in developing rat livers. Environ Toxicol. 30:712–723. 2015.PubMed/NCBI View Article : Google Scholar
6	Iida A, Shinoe T, Baba Y, Mano H and Watanabe S: Dicer plays essential roles for retinal development by regulation of survival and differentiation. Invest Ophthalmol Vis Sci. 52:3008–3017. 2011.PubMed/NCBI View Article : Google Scholar
7	Mohammad SM, Emadodin M and Hamed M: MiR-21: A key player in glioblastoma pathogenesis. J Cell Biochem. 119:1285–1290. 2018.PubMed/NCBI View Article : Google Scholar
8	Huang TZ, Wan XC, Alvarez AA, James CD, Song X, Yang Y, Sastry N, Nakano I, Sulman EP, Hu B and Cheng SY: MIR93 (microRNA-93) regulates tumorigenicity and therapy response of glioblastoma by targeting autophagy. Autophagy. 15:1100–1111. 2019.PubMed/NCBI View Article : Google Scholar
9	Chen L, Guan H, Gu C, Cao Y, Shao J and Wang F: miR-383 inhibits hepatocellular carcinoma cell proliferation via targeting APRIL. Tumour Biol. 37:2497–2507. 2016.PubMed/NCBI View Article : Google Scholar
10	Shang Y, Zang A, Li J, Jia Y, Li X, Zhang L, Huo R, Yang J, Feng J, Ge K, et al: MicroRNA-383 is a tumor suppressor and potential prognostic biomarker in human non-small cell lung caner. Biomed Pharmacother. 83:1175–1181. 2016.PubMed/NCBI View Article : Google Scholar
11	Zhao LN, Wang P, Liu YH, Cai H, Ma J, Liu LB, Xi Z, Li ZQ, Liu XB and Xue YX: MiR-383 inhibits proliferation, migration and angiogenesis of glioma-exposed endothelial cells in vitro via VEGF-mediated FAK and Src signaling pathways. Cell Signal. 30:142–153. 2017.PubMed/NCBI View Article : Google Scholar
12	Jiang MY, Han ZD, Li W, Yue F, Ye J, Li B, Cai Z, Lu JM, Dong W, Jiang X, et al: Mitochondrion-associated protein peroxiredoxin 3 promotes benign prostatic hyperplasia through autophagy suppression and pyroptosis activation. Oncotarget. 8:80295–80302. 2017.PubMed/NCBI View Article : Google Scholar
13	Magarin M, Pohl T, Lill A, Schulz H, Blaschke F, Heuser A, Thierfelder L, Donath S and Drenckhahn JD: Embryonic cardiomyocytes can orchestrate various cell protective mechanisms to survive mitochondrial stress. J Mol Cell Cardiol. 97:1–14. 2016.PubMed/NCBI View Article : Google Scholar
14	Song IS, Jeong YJ, Seo YJ, Byun JM, Kim YN, Jeong DH, Han J, Kim KT and Jang SW: Peroxiredoxin 3 maintains the survival of endometrial cancer stem cells by regulating oxidative stress. Oncotarget. 8:92788–92800. 2017.PubMed/NCBI View Article : Google Scholar
15	Li KK, Pang JC, Lau KM, Zhou L, Mao Y, Wang Y, Poon WS and Ng HK: MiR-383 is downregulated in medulloblastoma and targets peroxiredoxin 3 (PRDX3). Brain Pathol. 23:413–425. 2013.PubMed/NCBI View Article : Google Scholar
16	Srivastava RK, Li C, Ahmad A, Abrams O, Gorbatyuk MS, Harrod KS, Wek RC, Afaq F and Athar M: ATF4 regulates arsenic trioxide-mediated NADPH oxidase, ER-mitochondrial crosstalk and apoptosis. Arch Biochem Biophys. 609:39–50. 2016.PubMed/NCBI View Article : Google Scholar
17	Chen J, Stimpson SE, Fernandez-Bueno GA and Mathews CE: Mitochondrial reactive oxygen species and type 1 diabetes. Antioxid Redox Signal. 29:1361–1372. 2018.PubMed/NCBI View Article : Google Scholar
18	Holzerová E and Prokisch H: Mitochondria: Much ado about nothing? How dangerous is reactive oxygen species production? Int J Biochem Cell Biol. 63:16–20. 2015.PubMed/NCBI View Article : Google Scholar
19	Kornfeld OS, Hwang S, Disatnik MH, Chen CH, Qvit N and Mochly-Rosen D: Mitochondrial reactive oxygen species at the heart of the matter: New therapeutic approaches for cardiovascular diseases. Circ Res. 116:1783–1799. 2015.PubMed/NCBI View Article : Google Scholar
20	Liu KM, Chuang SM, Long CY, Lee YL, Wang CC, Lu MC, Lin RJ, Lu JH, Jang MY, Wu WJ, et al: Ketamine-induced ulcerative cystitis and bladder apoptosis involve oxidative stress mediated by mitochondria and the endoplasmic reticulum. Am J Physiol Renal Physiol. 309:F318–F331. 2015.PubMed/NCBI View Article : Google Scholar
21	Christen V, Camenzind M and Fent K: Silica nanoparticles induce endoplasmic reticulum stress response, oxidative stress and activate the mitogen-activated protein kinase (MAPK) signaling pathway. Toxicol Rep. 1:1143–1151. 2014.PubMed/NCBI View Article : Google Scholar
22	Cominacini L, Mozzini C, Garbin U, Pasini A, Stranieri C, Solani E, Vallerio P, Tinelli IA and Fratta Pasini A: Endoplasmic reticulum stress and Nrf2 signaling in cardiovascular diseases. Free Radic Biol Med. 88:233–242. 2015.PubMed/NCBI View Article : Google Scholar
23	Filomeni G, De Zio D and Cecconi F: Oxidative stress and autophagy: The clash between damage and metabolic needs. Cell Death Differ. 22:377–388. 2015.PubMed/NCBI View Article : Google Scholar
24	Muriach M, Flores-Bellver M, Romero FJ and Barcia JM: Diabetes and the brain: Oxidative stress, inflammation, and autophagy. Oxid Med Cell Longev. 2014(102158)2014.PubMed/NCBI View Article : Google Scholar
25	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.PubMed/NCBI View Article : Google Scholar
26	Basu A, Banerjee H, Rojas H, Martinez SR, Roy S, Jia Z, Lilly MB, De León M and Casiano CA: Differential expression of peroxiredoxins in prostate cancer: Consistent upregulation of PRDX3 and PRDX4. Prostate. 71:755–765. 2011.PubMed/NCBI View Article : Google Scholar
27	Moreira EF, Kantorow M and Rodriguez IR: Peroxiredoxin 3 (PDRX3) is highly expressed in the primate retina especially in blue cones. Exp Eye Res. 86:452–455. 2008.PubMed/NCBI View Article : Google Scholar
28	Whitaker HC, Patel D, Howat WJ, Warren AY, Kay JD, Sangan T, Marioni JC, Mitchell J, Aldridge S, Luxton HJ, et al: Peroxiredoxin-3 is overexpressed in prostate cancer and promotes cancer cell survival by protecting cells from oxidative stress. Br J Cancer. 109(983)2013.PubMed/NCBI View Article : Google Scholar
29	Lee YJ: Knockout mouse models for peroxiredoxins. Antioxidants (Basel). 9(182)2020.PubMed/NCBI View Article : Google Scholar
30	Lamb R, Ozsvari B, Lisanti CL, Tanowitz HB, Howell A, Martinez-Outschoorn UE, Sotgia F and Lisanti MP: Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: Treating cancer like an infectious disease. Oncotarget. 6:4569–4584. 2015.PubMed/NCBI View Article : Google Scholar
31	Li JZ, Ke Y, Misra HP, Trush MA, Li YR, Zhu H and Jia Z: Mechanistic studies of cancer cell mitochondria- and NQO1-mediated redox activation of beta-lapachone, a potentially novel anticancer agent. Toxicol Appl Pharmacol. 281:285–293. 2014.PubMed/NCBI View Article : Google Scholar
32	Vayalil PK, Oh JY, Zhou F, Diers AR, Smith MR, Golzarian H, Oliver PG, Smith RA, Murphy MP, Velu SE and Landar A: A novel class of mitochondria-targeted soft electrophiles modifies mitochondrial proteins and inhibits mitochondrial metabolism in breast cancer cells through redox mechanisms. PLoS One. 10(e0120460)2015.PubMed/NCBI View Article : Google Scholar
33	Hrycay EG and Bandiera SM: Involvement of cytochrome P450 in reactive oxygen species formation and cancer. Adv Pharmacol. 74:35–84. 2015.PubMed/NCBI View Article : Google Scholar
34	Doktorova H, Hrabeta J, Khalil MA and Eckschlager T: Hypoxia-induced chemoresistance in cancer cells: The role of not only HIF-1. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 159:166–177. 2015.PubMed/NCBI View Article : Google Scholar
35	Szarek E, Ball ER, Imperiale A, Tsokos M, Faucz FR, Giubellino A, Moussallieh FM, Namer IJ, Abu-Asab MS, Pacak K, et al: Carney triad, SDH-deficient tumors, and Sdhb^+/- mice share abnormal mitochondria. Endocr Relat Cancer. 22:345–352. 2015.PubMed/NCBI View Article : Google Scholar
36	Moloney JN and Cotter TG: ROS signalling in the biology of cancer. Semin Cell Dev Biol. 80:50–64. 2018.PubMed/NCBI View Article : Google Scholar
37	Pörn-Ares MI, Ares MP and Orrenius S: Calcium signalling and the regulation of apoptosis. Toxicol In Vitro. 12:539–543. 1998.PubMed/NCBI View Article : Google Scholar
38	Wu CH, Li J, Li L, Sun J, Fabbri M, Wayne AS, Seeger RC and Jong AY: Extracellular vesicles derived from natural killer cells use multiple cytotoxic proteins and killing mechanisms to target cancer cells. J Extracell Vesicles. 8(1588538)2019.PubMed/NCBI View Article : Google Scholar
39	Song IS, Kim HK, Jeong SH, Lee SR, Kim N, Rhee BD, Ko KS and Han J: Mitochondrial peroxiredoxin III is a potential target for cancer therapy. Int J Mol Sci. 12:7163–7185. 2011.PubMed/NCBI View Article : Google Scholar
40	Kudryavtseva AV, Krasnov GS, Dmitriev AA, Alekseev BY, Kardymon OL, Sadritdinova AF, Fedorova MS, Pokrovsky AV, Melnikova NV, Kaprin AD, et al: Mitochondrial dysfunction and oxidative stress in aging and cancer. Oncotarget. 7:44879–44905. 2016.PubMed/NCBI View Article : Google Scholar
41	Zhang YG, Wang L, Kaifu T, Li J, Li X and Li L: Accelerated decline of physical strength in peroxiredoxin-3 knockout mice. Exp Biol Med (Maywood). 241(1395)2016.PubMed/NCBI View Article : Google Scholar
42	Liu Z, Hu Y, Liang H, Sun Z, Feng S and Deng H: Silencing PRDX3 inhibits growth and promotes invasion and extracellular matrix degradation in hepatocellular carcinoma cells. J Proteome Res. 15:1506–1514. 2016.PubMed/NCBI View Article : Google Scholar
43	Azarbarzin S, Feizi MAH, Safaralizadeh R, Kazemzadeh M and Fateh A: The value of miR-383, an intronic miRNA, as a diagnostic and prognostic biomarker in intestinal-type gastric cancer. Biochem Genet. 55:244–252. 2017.PubMed/NCBI View Article : Google Scholar
44	Xu Z, Zeng X, Tian D, Xu H, Cai Q, Wang J and Chen Q: MicroRNA-383 inhibits anchorage-independent growth and induces cell cycle arrest of glioma cells by targeting CCND1. Biochem Biophys Res Commun. 453:833–838. 2014.PubMed/NCBI View Article : Google Scholar
45	Xu D, Ma P, Gao G, Gui Y, Niu X and Jin B: MicroRNA-383 expression regulates proliferation, migration, invasion, and apoptosis in human glioma cells. Tumor Biol. 36:7743–7753. 2015.PubMed/NCBI View Article : Google Scholar
46	Yin M, Wang X, Yao G, Lü M, Liang M, Sun Y and Sun F: Transactivation of micrornA-320 by microRNA-383 regulates granulosa cell functions by targeting E2F1 and SF-1 proteins. J Biol Chem. 289:18239–18257. 2014.PubMed/NCBI View Article : Google Scholar
47	Fateh A, Hosseinpour Feizi MA, Safaralizadeh R, Somi MH, Ravanbakhsh R, Shokoohi B, Hashemzadeh S and Azarbarzin S: Prognostic and predictive roles of microRNA-383 in colorectal cancer. Gastroenterol Insights. 7:1–14. 2016.