miR‑455 targets FABP4 to protect human endometrial stromal cells from cytotoxicity induced by hydrogen peroxide

Tang,Wenbo; Chen,Oujing; Yao,Fengxiang; Cui,Lining

doi:10.3892/mmr.2019.10727

miR‑455 targets FABP4 to protect human endometrial stromal cells from cytotoxicity induced by hydrogen peroxide

Authors:
- Wenbo Tang
- Oujing Chen
- Fengxiang Yao
- Lining Cui
View Affiliations

Affiliations: Department of Obstetrics and Gynecology, Ningbo First Hospital, Ningbo, Zhejiang 315000, P.R. China
Published online on: October 4, 2019 https://doi.org/10.3892/mmr.2019.10727
Pages: 4781-4790
Copyright: © Tang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Oxidative stress and dysregulation of antioxidant systems are associated with various complications in pregnancy. Endometriosis is a common gynecologic disease that affects women of reproductive age. Recent studies have indicated that oxidative stress may be involved in the pathophysiology of endometriosis. It has been reported that microRNAs can regulate the cellular response to oxidative stress, and mounting evidence indicates that fatty acid binding protein 4 (FABP4) plays an essential role in the regulation of systemic redox capacity. In the present study, we demonstrated that miR‑455 is a putative FABP4‑targeting miRNA. A luciferase activity assay revealed that miR‑455 can successfully bind to the 3'‑UTR of FABP4. Overexpression of miR‑455 led to the downregulation of FABP4 at both the mRNA and protein levels in a human endometrial stromal cell line. Then, the roles of miR‑455 and FABP4 in oxidative stress induced by hydrogen peroxide (H2O2) in human endometrial stromal cells were examined. We found that ectopic expression of miR‑455 protected cells from damage caused by H2O2. Further investigation found that forced expression of miR‑455 reduced the level of reactive oxygen species (ROS) and malondialdehyde (MDA), while the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH‑Px) were promoted. Silencing of FABP4 also generated cytoprotective effects against H2O2 in human endometrial stromal cells. Moreover, overexpression FABP4 abrogated the miR‑455‑mediated antioxidative stress effects in cells. Taken together, we propose that miR‑455 protects human endometrial stromal cells from oxidative stress at least partly via regulation of FABP4.

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1	Kennedy S, Bergqvist A, Chapron C, D'Hooghe T, Dunselman G, Greb R, Hummelshoj L, Prentice A and Saridogan E; ESHRE Special Interest Group for Endometriosis and Endometrium Guideline Development Group, : ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod. 20:2698–2704. 2005. View Article : Google Scholar : PubMed/NCBI
2	Sampson JA: Metastatic or embolic endometriosis, due to the menstrual dissemination of endometrial tissue into the venous circulation. Am J Pathol. 3:93–110.43. 1927.PubMed/NCBI
3	Sourial S, Tempest N and Hapangama DK: Theories on the pathogenesis of endometriosis. Int J Reprod Med. 2014:1795152014. View Article : Google Scholar : PubMed/NCBI
4	Vinatier D, Orazi G, Cosson M and Dufour P: Theories of endometriosis. Eur J Obstet Gynecol Reprod Biol. 96:21–34. 2001. View Article : Google Scholar : PubMed/NCBI
5	Christodoulakos G, Augoulea A, Lambrinoudaki I, Sioulas V and Creatsas G: Pathogenesis of endometriosis: The role of defective ‘immunosurveillance’. Eur J Contracept Reprod Health Care. 12:194–202. 2007. View Article : Google Scholar : PubMed/NCBI
6	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
7	Qin SB, Peng DY, Lu JM and Ke ZP: miR-182-5p inhibited oxidative stress and apoptosis triggered by oxidized low-density lipoprotein via targeting toll-like receptor 4. J Cell Physiol. 233:6630–6637. 2018. View Article : Google Scholar : PubMed/NCBI
8	Diao H, Liu B, Shi Y, Song C, Guo Z, Liu N, Song X, Lu Y, Lin X and Li Z: MicroRNA-210 alleviates oxidative stress-associated cardiomyocyte apoptosis by regulating BNIP3. Biosci Biotechnol Biochem. 81:1712–1720. 2017. View Article : Google Scholar : PubMed/NCBI
9	Hou M, Zuo X, Li C, Zhang Y and Teng Y: Mir-29b regulates oxidative stress by targeting SIRT1 in ovarian cancer cells. Cell Physiol Biochem. 43:1767–1776. 2017. View Article : Google Scholar : PubMed/NCBI
10	Zhang S, Wu W, Jiao G, Li C and Liu H: miR-455-3p activates Nrf2/ARE signaling via HDAC2 and protects osteoblasts from oxidative stress. Int J Biol Macromol. 107:2094–2101. 2018. View Article : Google Scholar : PubMed/NCBI
11	Xu D, Zhu H, Wang C, Zhu X, Liu G, Chen C and Cui Z: microRNA-455 targets cullin 3 to activate Nrf2 signaling and protect human osteoblasts from hydrogen peroxide. Oncotarget. 8:59225–59234. 2017.PubMed/NCBI
12	Furuhashi M and Hotamisligil GS: Fatty acid-binding proteins: Role in metabolic diseases and potential as drug targets. Nat Rev Drug Discov. 7:489–503. 2008. View Article : Google Scholar : PubMed/NCBI
13	Steen KA, Xu H and Bernlohr DA: FABP4/aP2 regulates macrophage redox signaling and inflammasome activation via control of UCP2. Mol Cell Biol. 37(pii): e00282–16. 2017.PubMed/NCBI
14	Kajimoto K, Minami Y and Harashima H: Cytoprotective role of the fatty acid binding protein 4 against oxidative and endoplasmic reticulum stress in 3T3-L1 adipocytes. FEBS Open Bio. 4:602–610. 2014. View Article : Google Scholar : PubMed/NCBI
15	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
16	Xu Y, Wang W, Jin K, Zhu Q, Lin H, Xie M and Wang D: Perillyl alcohol protects human renal tubular epithelial cells from hypoxia/reoxygenation injury via inhibition of ROS, endoplasmic reticulum stress and activation of PI3K/Akt/eNOS pathway. Biomed Pharmacother. 95:662–669. 2017. View Article : Google Scholar : PubMed/NCBI
17	Tsukahara H: Biomarkers for oxidative stress: Clinical application in pediatric medicine. Curr Med Chem. 14:339–351. 2007. View Article : Google Scholar : PubMed/NCBI
18	Halliwell B, Clement MV, Ramalingam J and Long LH: Hydrogen peroxide. Ubiquitous in cell culture and in vivo? IUBMB Life. 50:251–257. 2000. View Article : Google Scholar : PubMed/NCBI
19	Singh M, Sharma H and Singh N: Hydrogen peroxide induces apoptosis in HeLa cells through mitochondrial pathway. Mitochondrion. 7:367–373. 2007. View Article : Google Scholar : PubMed/NCBI
20	Clement MV, Ponton A and Pervaiz S: Apoptosis induced by hydrogen peroxide is mediated by decreased superoxide anion concentration and reduction of intracellular milieu. FEBS Lett. 440:13–18. 1998. View Article : Google Scholar : PubMed/NCBI
21	Degterev A, Boyce M and Yuan J: A decade of caspases. Oncogene. 22:8543–8567. 2003. View Article : Google Scholar : PubMed/NCBI
22	Thornberry NA: Caspases: A decade of death research. Cell Death Differ. 6:1023–1027. 1999. View Article : Google Scholar : PubMed/NCBI
23	Zal F, Khademi F, Taheri R and Mostafavi-Pour Z: Antioxidant ameliorating effects against H₂O₂-induced cytotoxicity in primary endometrial cells. Toxicol Mech Methods. 28:122–129. 2018. View Article : Google Scholar : PubMed/NCBI
24	Scutiero G, Iannone P, Bernardi G, Bonaccorsi G, Spadaro S, Volta CA, Greco P and Nappi L: Oxidative stress and endometriosis: A systematic review of the literature. Oxid Med Cell Longev. 2017:72652382017. View Article : Google Scholar : PubMed/NCBI
25	Yan J, Gong Y, She YM, Wang G, Roberts MS and Burczynski FJ: Molecular mechanism of recombinant liver fatty acid binding protein's antioxidant activity. J Lipid Res. 50:2445–2454. 2009. View Article : Google Scholar : PubMed/NCBI
26	Gong Y, Yu Z, Gao Y, Deng L, Wang M, Chen Y, Li J and Cheng B: FABP4 inhibitors suppress inflammation and oxidative stress in murine and cell models of acute lung injury. Biochem Biophys Res Commun. 496:1115–1121. 2018. View Article : Google Scholar : PubMed/NCBI
27	Rahman N, Jeon M and Kim YS: Methyl gallate, a potent antioxidant inhibits mouse and human adipocyte differentiation and oxidative stress in adipocytes through impairment of mitotic clonal expansion. Biofactors. 42:716–726. 2016. View Article : Google Scholar : PubMed/NCBI