High mobility group box 1-mediated autophagy promotes neuroblastoma cell chemoresistance

Wang,Li; Zhang,Huiping; Sun,Min; Yin,Zhanghua; Qian,Jihong

doi:10.3892/or.2015.4278

High mobility group box 1-mediated autophagy promotes neuroblastoma cell chemoresistance

Authors:
- Li Wang
- Huiping Zhang
- Min Sun
- Zhanghua Yin
- Jihong Qian
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Affiliations: Department of Neonatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China
Published online on: September 16, 2015 https://doi.org/10.3892/or.2015.4278
Pages: 2969-2976

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Abstract

Neuroblastoma (NB) is one of the most common tumors in childhood. Unfortunately, the survival outcomes remain unsatisfactory since NB commonly develops multidrug resistance. Recent studies have demonstrated that the high mobility group box 1 (HMGB1)-mediated autophagy promotes chemoresistance in osteosarcoma, lung adenocarcinoma and ovarian cancer, but the exact molecular mechanism underlying HMGB1-mediated autophagy in NB has not been clearly defined. In the present study, we investigated the role of HMGB1 in the development of resistance to anticancer agents in NB. Anticancer agents including doxorubicin, cisplatin and etoposide each induced HMGB1 upregulation, promoted cytosolic HMGB1 translocation and the elevation of autophagic activity in human NB cells. RNA interference-mediated knockdown of HMGB1 restored the chemosensitivity of NB cells. Furthermore, mechanistic investigation revealed that HMGB1 promoted the proliferative activity and invasive potential of NB cells. HMGB1 enhanced drug resistance by inducing Beclin-1-mediated autophagy, an intracellular self-defense mechanism known to confer drug resistance. In addition, we found that HMGB1 facilitated autophagic progression and reduced oxidative stress induced by doxorubicin. Therefore, through its role as a regulator of autophagy, HMGB1 is a critical factor in the development of chemoresistance and tumorigenesis, and it may be a novel target for improving the efficacy of NB therapy.

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1	Biedler JL: Drug resistance: Genotype versus phenotype - thirty-second G. H. A. Clowes Memorial Award Lecture. Cancer Res. 54:666–678. 1994.PubMed/NCBI
2	Michaelis M, Klassert D, Barth S, Suhan T, Breitling R, Mayer B, Hinsch N, Doerr HW, Cinatl J and Cinatl J Jr: Chemoresistance acquisition induces a global shift of expression of aniogenesis-associated genes and increased pro-angogenic activity in neuroblastoma cells. Mol Cancer. 8:802009. View Article : Google Scholar : PubMed/NCBI
3	Furfaro AL, Piras S, Passalacqua M, Domenicotti C, Parodi A, Fenoglio D, Pronzato MA, Marinari UM, Moretta L, Traverso N, et al: HO-1 up-regulation: A key point in high-risk neuroblastoma resistance to bortezomib. Biochim Biophys Acta. 1842:613–622. 2014. View Article : Google Scholar : PubMed/NCBI
4	Zhang Y, Cheng Y, Ren X, Zhang L, Yap KL, Wu H, Patel R, Liu D, Qin ZH, Shih IM, et al: NAC1 modulates sensitivity of ovarian cancer cells to cisplatin by altering the HMGB1-mediated autophagic response. Oncogene. 31:1055–1064. 2012. View Article : Google Scholar :
5	Yang S, Xu L, Yang T and Wang F: High-mobility group box-1 and its role in angiogenesis. J Leukoc Biol. 95:563–574. 2014. View Article : Google Scholar : PubMed/NCBI
6	Tang D, Kang R, Cheh CW, Livesey KM, Liang X, Schapiro NE, Benschop R, Sparvero LJ, Amoscato AA, Tracey KJ, et al: HMGB1 release and redox regulates autophagy and apoptosis in cancer cells. Oncogene. 29:5299–5310. 2010. View Article : Google Scholar : PubMed/NCBI
7	Zhang L, Han J, Wu H, Liang X, Zhang J, Li J, Xie L, Xie Y, Sheng X and Yu J: The association of HMGB1 expression with clinicopathological significance and prognosis in hepatocellular carcinoma: A meta-analysis and literature review. PLoS One. 9:e1106262014. View Article : Google Scholar : PubMed/NCBI
8	Süren D, Yıldırım M, Demirpençe Ö, Kaya V, Alikanoğlu AS, Bülbüller N, Yıldız M and Sezer C: The role of high mobility group box 1 (HMGB1) in colorectal cancer. Med Sci Monit. 20:530–537. 2014. View Article : Google Scholar : PubMed/NCBI
9	Meyer A, Staratschek-Jox A, Springwald A, Wenk H, Wolf J, Wickenhauser C and Bullerdiek J: Non-Hodgkin lymphoma expressing high levels of the danger-signalling protein HMGB1. Leuk Lymphoma. 49:1184–1189. 2008. View Article : Google Scholar : PubMed/NCBI
10	Brezniceanu ML, Völp K, Bösser S, Solbach C, Lichter P, Joos S and Zörnig M: HMGB1 inhibits cell death in yeast and mammalian cells and is abundantly expressed in human breast carcinoma. FASEB J. 17:1295–1297. 2003.PubMed/NCBI
11	Wu D, Ding Y, Wang S, Zhang Q and Liu L: Increased expression of high mobility group box 1 (HMGB1) is associated with progression and poor prognosis in human nasopharyngeal carcinoma. J Pathol. 216:167–175. 2008. View Article : Google Scholar : PubMed/NCBI
12	Ueda M, Takahashi Y, Shinden Y, Sakimura S, Hirata H, Uchi R, Takano Y, Kurashige J, Iguchi T, Eguchi H, et al: Prognostic significance of high mobility group box 1 (HMGB1) expression in patients with colorectal cancer. Anticancer Res. 34:5357–5362. 2014.PubMed/NCBI
13	Chen J, Liu X, Zhang J and Zhao Y: Targeting HMGB1 inhibits ovarian cancer growth and metastasis by lentivirus-mediated RNA interference. J Cell Physiol. 227:3629–3638. 2012. View Article : Google Scholar : PubMed/NCBI
14	Fu LL, Cheng Y and Liu B: Beclin-1: Autophagic regulator and therapeutic target in cancer. Int J Biochem Cell Biol. 45:921–924. 2013. View Article : Google Scholar : PubMed/NCBI
15	Tang D, Kang R, Livesey KM, Cheh CW, Farkas A, Loughran P, Hoppe G, Bianchi ME, Tracey KJ, Zeh HJ III, et al: Endogenous HMGB1 regulates autophagy. J Cell Biol. 190:881–892. 2010. View Article : Google Scholar : PubMed/NCBI
16	Tang D, Kang R, Livesey KM, Kroemer G, Billiar TR, Van Houten B, Zeh HJ III and Lotze MT: High-mobility group box 1 is essential for mitochondrial quality control. Cell Metab. 13:701–711. 2011. View Article : Google Scholar : PubMed/NCBI
17	Huang J, Ni J, Liu K, Yu Y, Xie M, Kang R, Vernon P, Cao L and Tang D: HMGB1 promotes drug resistance in osteosarcoma. Cancer Res. 72:230–238. 2012. View Article : Google Scholar
18	Pan B, Chen D, Huang J, Wang R, Feng B, Song H and Chen L: HMGB1-mediated autophagy promotes docetaxel resistance in human lung adenocarcinoma. Mol Cancer. 13:1652014. View Article : Google Scholar : PubMed/NCBI
19	Yang YH, Chen K, Li B, Chen JW, Zheng XF, Wang YR, Jiang SD and Jiang LS: Estradiol inhibits osteoblast apoptosis via promotion of autophagy through the ER-ERK-mTOR pathway. Apoptosis. 18:1363–1375. 2013. View Article : Google Scholar : PubMed/NCBI
20	Wang L, Zhang H, Qian J, Wang K and Zhu J: Interleukin-10 blocks in vitro replication of human cytomegalovirus by inhibiting the virus-induced autophagy in MRC5 cells. Biochem Biophys Res Commun. 448:448–453. 2014. View Article : Google Scholar : PubMed/NCBI
21	Yang YH, Li B, Zheng XF, Chen JW, Chen K, Jiang SD and Jiang LS: Oxidative damage to osteoblasts can be alleviated by early autophagy through the endoplasmic reticulum stress pathway - implications for the treatment of osteoporosis. Free Radic Biol Med. 77:10–20. 2014. View Article : Google Scholar : PubMed/NCBI
22	Murai T, Nakagawa Y, Maeda H and Terada K: Altered regulation of cell cycle machinery involved in interleukin-1-induced G₁ and G₂ phase growth arrest of A375S2 human melanoma cells. J Biol Chem. 276:6797–6806. 2001. View Article : Google Scholar
23	Petiot A, Ogier-Denis E, Blommaart EF, Meijer AJ and Codogno P: Distinct classes of phosphatidylinositol 3′-kinases are involved in signaling pathways that control macroautophagy in HT-29 cells. J Biol Chem. 275:992–998. 2000. View Article : Google Scholar : PubMed/NCBI
24	Moreira AC, Branco AF, Sampaio SF, Cunha-Oliveira T, Martins TR, Holy J, Oliveira PJ and Sardão VA: Mitochondrial apoptosis-inducing factor is involved in doxorubicin-induced toxicity on H9c2 cardiomyoblasts. Biochim Biophys Acta. 1842:2468–2478. 2014. View Article : Google Scholar : PubMed/NCBI
25	Singla S, Kumar NR and Kaur J: In vivo studies on the protective effect of propolis on doxorubicin-induced toxicity in liver of male rats. Toxicol Int. 21:191–195. 2014. View Article : Google Scholar : PubMed/NCBI
26	Shokoohinia Y, Hosseinzadeh L, Moieni-Arya M, Mostafaie A and Mohammadi-Motlagh HR: Osthole attenuates doxorubicin-induced apoptosis in PC12 cells through inhibition of mitochondrial dysfunction and ROS production. Biomed Res Int. 2014:1568482014. View Article : Google Scholar : PubMed/NCBI
27	Tonini GP and Pistoia V: Molecularly guided therapy of neuroblastoma: A review of different approaches. Curr pharm Des. 12:2303–2317. 2006. View Article : Google Scholar : PubMed/NCBI
28	Guazzi S, Strangio A, Franzi AT and Bianchi ME: HMGB1, an architectural chromatin protein and extracellular signalling factor, has a spatially and temporally restricted expression pattern in mouse brain. Gene Expr Patterns. 3:29–33. 2003. View Article : Google Scholar : PubMed/NCBI
29	Faraco G, Fossati S, Bianchi ME, Patrone M, Pedrazzi M, Sparatore B, Moroni F and Chiarugi A: High mobility group box 1 protein is released by neural cells upon different stresses and worsens ischemic neurodegeneration in vitro and in vivo. J Neurochem. 103:590–603. 2007. View Article : Google Scholar : PubMed/NCBI
30	Reismann M, Wehrmann F, Schukfeh N, Kuebler JF, Ure B and Glüer S: Carbon dioxide, hypoxia and low pH lead to overexpression of c-myc and HMGB-1 oncogenes in neuroblastoma cells. Eur J Pediatr Surg. 19:224–227. 2009. View Article : Google Scholar : PubMed/NCBI
31	Pedrazzi M, Averna M, Sparatore B, Patrone M, Salamino F, Marcoli M, Maura G, Cervetto C, Frattaroli D, Pontremoli S, et al: Potentiation of NMDA receptor-dependent cell responses by extracellular high mobility group box 1 protein. PLoS One. 7:e445182012. View Article : Google Scholar : PubMed/NCBI
32	Wittig JC, Bickels J, Priebat D, Jelinek J, Kellar-Graney K, Shmookler B and Malawer MM: Osteosarcoma: A multi-disciplinary approach to diagnosis and treatment. Am Fam Physician. 65:1123–1132. 2002.PubMed/NCBI
33	Mohan N, Chakrabarti M, Banik NL and Ray SK: Combination of LC3 shRNA plasmid transfection and genistein treatment inhibited autophagy and increased apoptosis in malignant neuroblastoma in cell culture and animal models. PLoS One. 8:e789582013. View Article : Google Scholar : PubMed/NCBI
34	Degenhardt K, Mathew R, Beaudoin B, Bray K, Anderson D, Chen G, Mukherjee C, Shi Y, Gélinas C, Fan Y, et al: Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell. 10:51–64. 2006. View Article : Google Scholar : PubMed/NCBI
35	Lockshin RA and Zakeri Z: Apoptosis, autophagy, and more. Int J Biochem Cell Biol. 36:2405–2419. 2004. View Article : Google Scholar : PubMed/NCBI
36	Zhao Z, Tao L, Shen C, Liu B, Yang Z and Tao H: Silencing of Barkor/ATG14 sensitizes osteosarcoma cells to cisplatin-induced apoptosis. Int J Mol Med. 33:271–276. 2014.
37	Lanvers-Kaminsky C, Winter B, Koling S, Frodermann B, Braun Y, Schaefer KL, Diallo R, Koenemann S, Wai D, Willich N, et al: Doxorubicin modulates telomerase activity in Ewing's sarcoma in vitro and in vivo. Oncol Rep. 14:751–758. 2005.PubMed/NCBI
38	Zhou Y, Sun K, Ma Y, Yang H, Zhang Y, Kong X and Wei L: Autophagy inhibits chemotherapy-induced apoptosis through downregulating Bad and Bim in hepatocellular carcinoma cells. Sci Rep. 4:53822014.PubMed/NCBI