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Protein & Peptide Letters

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ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

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Research Article

Role of BLACAT1 in IL-1β-Induced Human Articular Chondrocyte Apoptosis and Extracellular Matrix Degradation via the miR-149-5p/ HMGCR Axis

Author(s): Zhiquan Li, Yingchun Wang, Yaoping Wu, Yanwu Liu, Yinan Zhao, Xiaochao Chen, Mo Li* and Rui Zhao*

Volume 29, Issue 7, 2022

Published on: 02 August, 2022

Page: [584 - 594] Pages: 11

DOI: 10.2174/0929866529666220602094940

Price: $65

Abstract

Background: Osteoarthritis (OA) is an inflammatory joint disorder with high incidence rates. Long non-coding RNAs (LncRNAs) influence OA development.

Objectives: In this research, we attempt to figure out the functions of lncRNA BLACAT1 in human articular chondrocyte (HAC) apoptosis and extracellular matrix (ECM) degradation in OA.

Methods: Interleukin (IL)-1β was employed to induce HAC damage. Cell viability and apoptosis were detected, with expression patterns of lncRNA BLACAT1, miR-149-5p, and HMGCR, and levels of Caspase-3, Caspase-9, BAX, Bcl-2, COL2A1, and SOX9 determined. Then, lncRNA BLACAT1 was silenced in IL-1β-treated HACs to analyze its role in HAC damage. The target relations of lncRNA BLACAT1 and miR-149-5p and miR-149-5p and HMGCR were verified. In addition, combined experiments were performed as a miR-149-5p inhibitor or HMGCR overexpression was injected into cells with lncRNA BLACAT1 silencing.

Results: In IL-1β-treated HACs, lncRNA BLACAT1 and HMGCR were overexpressed while miR- 149-5p was poorly expressed, along with reduced cell viability, enhanced apoptosis, elevated Caspase-3 and Caspase-9 activities, increased BAX level, decreased Bcl-2 level, and declined levels of COL2A1 and SOX9, which were reversed by lncRNA BLACAT1 silencing. LncRNA BLACAT1 targeted miR-149-5p, and miR-149-5p targeted HMGCR. miR-149-5p knockout or HMGCR overexpression annulled the inhibitory role of lncRNA BLACAT1 silencing in HAC apoptosis and ECM degradation.

Conclusion: LncRNA BLACAT1 was overexpressed in IL-1β-treated HACs, and the lncRNA BLACAT1/miR-149-5p/HMGCR ceRNA network promoted HAC apoptosis and ECM degradation.

Keywords: Osteoarthritis, articular chondrocytes, apoptosis, IL-1β, extracellular matrix, LncRNA BLACAT1, miR-149-5p, HMGCR.

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[1]
Barg, A.; Pagenstert, G.I.; Hügle, T.; Gloyer, M.; Wiewiorski, M.; Henninger, H.B.; Valderrabano, V. Ankle osteoarthritis: Etiology, diagnostics, and classification. Foot Ankle Clin., 2013, 18(3), 411-426.
[http://dx.doi.org/10.1016/j.fcl.2013.06.001] [PMID: 24008208]
[2]
Mandl, L.A. Osteoarthritis year in review 2018: Clinical. Osteoarthritis Cartilage, 2019, 27(3), 359-364.
[http://dx.doi.org/10.1016/j.joca.2018.11.001] [PMID: 30453055]
[3]
Yunus, M.H.M.; Nordin, A.; Kamal, H. Pathophysiological perspective of osteoarthritis. Medicina (Kaunas), 2020, 56(11), E614.
[http://dx.doi.org/10.3390/medicina56110614] [PMID: 33207632]
[4]
Knapik, J.J.; Pope, R.; Orr, R.; Schram, B. Osteoarthritis: Pathophysiology, prevalence, risk factors, and exercise for reducing pain and disability. J. Spec. Oper. Med., 2018, 18(3), 94-102.
[PMID: 30222846]
[5]
Charlier, E.; Deroyer, C.; Ciregia, F.; Malaise, O.; Neuville, S.; Plener, Z.; Malaise, M.; de Seny, D. Chondrocyte dedifferentiation and osteoarthritis (OA). Biochem. Pharmacol., 2019, 165, 49-65.
[6]
Hwang, H.S.; Kim, H.A. Chondrocyte apoptosis in the pathogenesis of osteoarthritis. Int. J. Mol. Sci., 2015, 16(11), 26035-26054.
[http://dx.doi.org/10.3390/ijms161125943] [PMID: 26528972]
[7]
Rahmati, M.; Nalesso, G.; Mobasheri, A.; Mozafari, M. Aging and osteoarthritis: Central role of the extracellular matrix. Ageing Res. Rev., 2017, 40, 20-30.
[8]
Zhu, J.; Yu, W.; Wang, Y.; Xia, K.; Huang, Y.; Xu, A.; Chen, Q.; Liu, B.; Tao, H.; Li, F.; Liang, C. lncRNAs: Function and mechanism in cartilage development, degeneration, and regeneration. Stem Cell Res. Ther., 2019, 10(1), 344.
[http://dx.doi.org/10.1186/s13287-019-1458-8] [PMID: 31753016]
[9]
Ji, Y.; Fang, Q.Y.; Wang, S.N.; Zhang, Z.W.; Hou, Z.J.; Li, J.N.; Fu, S.Q. Lnc-RNA BLACAT1 regulates differentiation of bone marrow stromal stem cells by targeting miR-142-5p in osteoarthritis. Eur. Rev. Med. Pharmacol. Sci., 2020, 24(6), 2893-2901.
[PMID: 32271407]
[10]
Lu, H.; Liu, H.; Yang, X.; Ye, T.; Lv, P.; Wu, X.; Ye, Z. LncRNA BLACAT1 may serve as a prognostic predictor in cancer: Evidence from a meta-analysis. Biomed. Res. Int., 2019, 2019, 1275491.
[11]
Chen, R.; Zhou, S.; Chen, J.; Lin, S.; Ye, F.; Jiang, P. LncRNA BLACAT1/miR-519d-3p/CREB1 axis mediates proliferation, apoptosis, migration, invasion, and drug-resistance in colorectal cancer progression. Cancer Manag. Res., 2020, 12, 13137-48.
[12]
Xie, F.; Liu, Y.L.; Chen, X.Y.; Li, Q.; Zhong, J.; Dai, B.Y.; Shao, X.F.; Wu, G.B. Role of MicroRNA, LncRNA, and exosomes in the progression of osteoarthritis: A review of recent literature. Orthop. Surg., 2020, 12(3), 708-716.
[http://dx.doi.org/10.1111/os.12690] [PMID: 32436304]
[13]
Wang, W.; Han, X.; Zhao, T.; Zhang, X.; Qu, P.; Zhao, H. AGT, targeted by miR-149-5p, promotes IL-6-induced inflammatory responses of chondrocytes in osteoarthritis via activating JAK2/STAT3 pathway. Clin. Exp. Rheumatol., 2020, 38(6), 1088-1095.
[PMID: 32141427]
[14]
Liu, Y.; Liu, K.; Tang, C.; Shi, Z.; Jing, K.; Zheng, J. Long non-coding RNA XIST contributes to osteoarthritis progression via miR-149-5p/DNMT3A axis. Biomed. Pharmacother., 2020, 128, 110349.
[15]
Yu, F.; Zeng, H.; Lei, M.; Xiao, D.M.; Li, W.; Yuan, H.; Lin, J.J. Effects of SIRT1 gene knock-out via activation of SREBP2 protein-mediated PI3K/AKT signaling on osteoarthritis in mice. J. Huazhong Univ. Sci. Technol. Med. Sci., 2016, 36(5), 683-690.
[http://dx.doi.org/10.1007/s11596-016-1645-0] [PMID: 27752896]
[16]
Hua, H.; Yang, T.; Huang, L.; Chen, R.; Li, M.; Zou, Z.; Wang, N.; Yang, D.; Liu, Y. Protective effects of lanosterol synthase up-regulation in UV-B-induced oxidative stress. Front. Pharmacol., 2019, 10, 947.
[http://dx.doi.org/10.3389/fphar.2019.00947]
[17]
Shen, X.F.; Cheng, Y.; Dong, Q.R.; Zheng, M.Q. MicroRNA-675-3p regulates IL-1β-stimulated human chondrocyte apoptosis and cartilage degradation by targeting GNG5. Biochem. Biophys. Res. Commun., 2020, 527(2), 458-465.
[http://dx.doi.org/10.1016/j.bbrc.2020.04.044] [PMID: 32336544]
[18]
Wang, B.W.; Jiang, Y.; Yao, Z.L.; Chen, P.S.; Yu, B.; Wang, S.N. Aucubin protects chondrocytes against IL-1beta-Induced apoptosis in vitro and inhibits osteoarthritis in mice model. Drug Des. Devel. Ther., 2019, 13, 3529-38.
[19]
Cao, Z.; Pan, X.; Yang, Y.; Huang, Y.; Shen, H.B. The lncLocator: A subcellular localization predictor for long non-coding RNAs based on a stacked ensemble classifier. Bioinformatics, 2018, 34(13), 2185-2194.
[http://dx.doi.org/10.1093/bioinformatics/bty085] [PMID: 29462250]
[20]
Li, J.H.; Liu, S.; Zhou, H.; Qu, L.H.; Yang, J.H. starBase v2.0: Decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res., 2014, 42, D92-D97.
[http://dx.doi.org/10.1093/nar/gkt1248] [PMID: 24297251]
[21]
Agarwal, V.; Bell, G.W.; Nam, J.W.; Bartel, D.P. Predicting effective microRNA target sites in mammalian mRNAs. eLife, 2015, 4, 4.
[http://dx.doi.org/10.7554/eLife.05005] [PMID: 26267216]
[22]
Chen, Y.; Wang, X. miRDB: An online database for prediction of functional microRNA targets. Nucleic Acids Res., 2020, 48(D1), D127-D131.
[http://dx.doi.org/10.1093/nar/gkz757] [PMID: 31504780]
[23]
Wang, R.; Li, W.; Bordewijk, E.M.; Legro, R.S.; Zhang, H.; Wu, X.; Gao, J.; Morin-Papunen, L.; Homburg, R.; König, T.E.; Moll, E.; Kar, S.; Huang, W.; Johnson, N.P.; Amer, S.A.; Vegetti, W.; Palomba, S.; Falbo, A.; Özmen, Ü.; Nazik, H.; Williams, C.D.; Federica, G.; Lord, J.; Sahin, Y.; Bhattacharya, S.; Norman, R.J.; van Wely, M.; Mol, B.W. First-line ovulation induction for polycystic ovary syndrome: An individual participant data meta-analysis. Hum. Reprod. Update, 2019, 25(6), 717-732.
[http://dx.doi.org/10.1093/humupd/dmz029] [PMID: 31647106]
[24]
Musumeci, G.; Castrogiovanni, P.; Trovato, F.M.; Weinberg, A.M.; Al-Wasiyah, M.K.; Alqahtani, M.H.; Mobasheri, A. Biomarkers of chondrocyte apoptosis and autophagy in osteoarthritis. Int. J. Mol. Sci., 2015, 16(9), 20560-20575.
[http://dx.doi.org/10.3390/ijms160920560] [PMID: 26334269]
[25]
Wang, Z.; Liu, X.; Liu, X.; Niu, D. Long non-coding RNA BLACAT1 promotes the tumorigenesis of gastric cancer by sponging microRNA-149-5p and targeting KIF2A. Cancer Manag. Res., 2020, 12, 6629-40.
[http://dx.doi.org/10.2147/CMAR.S258178]
[26]
Kostopoulou, F.; Gkretsi, V.; Malizos, K.N.; Iliopoulos, D.; Oikonomou, P.; Poultsides, L.; Tsezou, A. Central role of SREBP-2 in the pathogenesis of osteoarthritis. PLoS One, 2012, 7(5), e35753.
[http://dx.doi.org/10.1371/journal.pone.0035753] [PMID: 22662110]
[27]
Ding, Y.; Wang, L.; Zhao, Q.; Wu, Z.; Kong, L. MicroRNA-93 inhibits chondrocyte apoptosis and inflammation in osteoarthritis by targeting the TLR4/NF-κB signaling pathway. Int. J. Mol. Med., 2019, 43(2), 779-790.
[PMID: 30569118]
[28]
Theocharis, A.D.; Manou, D.; Karamanos, N.K. The extracellular matrix as a multitasking player in disease. FEBS J., 2019, 286(15), 2830-2869.
[http://dx.doi.org/10.1111/febs.14818] [PMID: 30908868]
[29]
Jiang, S.D.; Lu, J.; Deng, Z.H.; Li, Y.S.; Lei, G.H. Long noncoding RNAs in osteoarthritis. Joint Bone Spine, 2017, 84(5), 553-556.
[http://dx.doi.org/10.1016/j.jbspin.2016.09.006] [PMID: 27919571]
[30]
Lao, M.X.; Xu, H.S. Involvement of long non-coding RNAs in the pathogenesis of rheumatoid arthritis. Chin. Med. J. (Engl.), 2020, 133(8), 941-950.
[http://dx.doi.org/10.1097/CM9.0000000000000755] [PMID: 32187055]
[31]
Ye, T.; Yang, X.; Liu, H.; Lv, P.; Ye, Z. Long non-coding RNA BLACAT1 in human cancers. OncoTargets Ther., 2020, 13, 8263-72.
[http://dx.doi.org/10.2147/OTT.S261461]
[32]
Aghaei, M.; KhanAhmad, H.; Aghaei, S.; Ali Nilforoushzadeh, M.; Mohaghegh, M.A.; Hejazi, S.H. The role of Bax in the apoptosis of Leishmania-infected macrophages. Microb. Pathog., 2020, 139, 103892.
[http://dx.doi.org/10.1016/j.micpath.2019.103892] [PMID: 31778755]
[33]
Dietrich, J.B. Apoptosis and anti-apoptosis genes in the Bcl-2 family. Arch. Physiol. Biochem., 1997, 105(2), 125-135.
[http://dx.doi.org/10.1076/apab.105.2.125.12927] [PMID: 9296841]
[34]
Okazaki, K.; Sandell, L.J. Extracellular matrix gene regulation. Clin. Orthop. Relat. Res., 2004, (427)(Suppl.), S123-S128.
[http://dx.doi.org/10.1097/01.blo.0000144478.51284.f3] [PMID: 15480054]
[35]
Xia, H.; Cao, D.; Yang, F.; Yang, W.; Li, W.; Liu, P.; Wang, S.; Yang, F. Jiawei Yanghe decoction ameliorates cartilage degradation in vitro and vivovia Wnt/β-catenin signaling pathway. Biomed. Pharmacother., 2020, 122, 109708.
[http://dx.doi.org/10.1016/j.biopha.2019.109708] [PMID: 31918279]
[36]
Niu, D.; Wang, L.; Cui, J.; Zhou, B.; Yao, L. Inhibition of long noncoding RNA BLACAT1 protects anesthesia-induced neural cytotoxicity in human induced pluripotent stem cells derived neurons. Eur. J. Pharmacol., 2019, 865, 172737.
[http://dx.doi.org/10.1016/j.ejphar.2019.172737]
[37]
Chen, Y.; Lin, Y.; Bai, Y.; Cheng, D.; Bi, Z. A Long Noncoding RNA (lncRNA)-associated competing endogenous RNA (ceRNA) network identifies eight lncRNA biomarkers in patients with osteoarthritis of the knee. Med. Sci. Monit., 2019, 25, 2058-65.
[38]
Swingler, T.E.; Niu, L.; Smith, P.; Paddy, P.; Le, L.; Barter, M.J.; Young, D.A.; Clark, I.M. The function of microRNAs in cartilage and osteoarthritis. Clin. Exp. Rheumatol., 2019, 120(5), 40-7.
[39]
Law, Y.Y.; Lee, W.F.; Hsu, C.J.; Lin, Y.Y.; Tsai, C.H.; Huang, C.C.; Wu, M.H.; Tang, C.H.; Liu, J.F. miR-let-7c-5p and miR-149-5p inhibit proinflammatory cytokine production in osteoarthritis and rheumatoid arthritis synovial fibroblasts. Aging (Albany NY), 2021, 13(13), 17227-17236.
[http://dx.doi.org/10.18632/aging.203201] [PMID: 34198264]
[40]
Fu, S.; Fan, Q.; Xu, J.; Yu, S.; Sun, M.; Ji, Y.; Liu, D. Circ_0008956 contributes to IL-1beta-induced osteoarthritis progression via miR-149-5p/NAMPT axis. Int. Immunopharmacol., 2021, 98, 107857.
[41]
Grieco, F.A.; Sebastiani, G.; Juan-Mateu, J.; Villate, O.; Marroqui, L.; Ladrière, L.; Tugay, K.; Regazzi, R.; Bugliani, M.; Marchetti, P.; Dotta, F.; Eizirik, D.L. MicroRNAs miR-23a-3p, miR-23b-3p, and miR-149-5p regulate the expression of proapoptotic BH3-Only proteins DP5 and PUMA in human pancreatic β-cells. Diabetes, 2017, 66(1), 100-112.
[http://dx.doi.org/10.2337/db16-0592] [PMID: 27737950]
[42]
Chiu, Y.S.; Bamodu, O.A.; Fong, I.H.; Lee, W.H.; Lin, C.C.; Lu, C.H.; Yeh, C.T. The JAK inhibitor Tofacitinib inhibits structural damage in osteoarthritis by modulating JAK1/TNF-alpha/IL-6 signaling through Mir-149-5p. Bone, 2021, 151, 116024.
[43]
Liu, Y.; Yang, H.; Song, Z.; Gu, S. Copper excess in liver HepG2 cells interferes with apoptosis and lipid metabolic signaling at the protein level. Turk. J. Gastroenterol., 2014, 25, 116-21.
[44]
Saeed, K.; Shah, S.A.; Ullah, R.; Alam, S.I.; Park, J.S.; Saleem, S.; Jo, M.H.; Kim, M.W.; Hahm, J.R.; Kim, M.O. Quinovic acid impedes cholesterol dyshomeostasis, oxidative stress, and neurodegeneration in an amyloid-beta-induced mouse model. Oxid. Med. Cell. Longev., 2020, 2020, 9523758.
[45]
Kurashige, T.; Murao, T.; Mine, N.; Sugiura, T.; Inazuka, Y.; Kuraoka, K.; Takahashi, T.; Maruyama, H.; Torii, T. Anti-HMGCR antibody-positive myopathy shows Bcl-2-Positive inflammation and lymphocytic accumulations. J. Neuropathol. Exp. Neurol., 2020, 79(4), 448-457.
[http://dx.doi.org/10.1093/jnen/nlaa006] [PMID: 32100014]

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