CISD2 promotes the proliferation of glioma cells via suppressing beclin‑1‑mediated autophagy and is targeted by microRNA‑449a

Sun,Ai‑Gang; Meng,Fan‑Guo; Wang,Ming‑Guang

doi:10.3892/mmr.2017.7642

CISD2 promotes the proliferation of glioma cells via suppressing beclin‑1‑mediated autophagy and is targeted by microRNA‑449a

Authors:
- Ai‑Gang Sun
- Fan‑Guo Meng
- Ming‑Guang Wang
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Affiliations: Department of Neurosurgery, The People's Hospital of Linyi, Linyi, Shandong 276003, P.R. China
Published online on: September 27, 2017 https://doi.org/10.3892/mmr.2017.7642
Pages: 7939-7948
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

CDGSH iron sulfur domain 2 (CISD2) has been found to be important in carcinogenesis. However, the role of CISD2 in glioma remains to be elucidated. The present study aimed to investigate the role of CISD2 in glioma using the reverse transcription‑quantitative polymerase chain reaction, western blotting, co‑immunoprecipitation assay, immunofluorescence staining and other methods. The results demonstrated that the mRNA and protein levels of CISD2 were found to be upregulated in glioma tissues, compared with the levels in matched normal tissues. Clinical data analysis showed that the level of CISD2 was negatively correlated with the survival rates of patients with glioma. In addition, high levels of CISD2 were associated with advanced clinical stage, relapse, vascular invasion and increased tumor size. The inhibition of CISD2 suppressed the proliferation and survival of glioma cells in vitro and in vivo. Mechanistically, it was found that small interfering RNA‑induced knock down of CISD2 inhibited the proliferation of glioma cells through activating beclin‑1‑mediated autophagy. The results also revealed that CISD2 was a target of microRNA (miR)‑449a. Together, the results of the present study demonstrated that CISD2 was increased in glioma samples and was associated with poor prognosis and aggressive tumor behavior. The miR‑449a/CISD2/beclin‑1‑mediated autophagy regulatory network contributed to the proliferation of glioma cells. Targeting this pathway may be a promising strategy for glioma therapy.

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1	Chen Y, Wu Y, Huang X, Qu P, Li G, Jin T, Xing J and He S: Leukocyte telomere length: A novel biomarker to predict the prognosis of glioma patients. J Cancer Res Clin Oncol. 141:1739–1747. 2015. View Article : Google Scholar : PubMed/NCBI
2	Wachsberger PR, Lawrence YR, Liu Y, Rice B, Feo N, Leiby B and Dicker AP: Hsp90 inhibition enhances PI-3 kinase inhibition and radiosensitivity in glioblastoma. J Cancer Res Clin Oncol. 140:573–582. 2014. View Article : Google Scholar : PubMed/NCBI
3	Gulati S, Jakola AS, Johannesen TB and Solheim O: Survival and treatment patterns of glioblastoma in the elderly: A population-based study. World Neurosurg. 78:518–526. 2012. View Article : Google Scholar : PubMed/NCBI
4	Fukushima T, Kawaguchi M, Yorita K, Tanaka H, Takeshima H, Umezawa K and Kataoka H: Antitumor effect of dehydroxymethylepoxyquinomicin, a small molecule inhibitor of nuclear factor-κB, on glioblastoma. Neuro Oncol. 14:19–28. 2012. View Article : Google Scholar : PubMed/NCBI
5	Lin J, Zhang L, Lai S and Ye K: Structure and molecular evolution of CDGSH iron-sulfur domains. PLoS One. 6:e247902011. View Article : Google Scholar : PubMed/NCBI
6	Wu CY, Chen YF, Wang CH, Kao CH, Zhuang HW, Chen CC, Chen LK, Kirby R, Wei YH, Tsai SF and Tsai TF: A persistent level of Cisd2 extends healthy lifespan and delays aging in mice. Hum Mol Genet. 21:3956–3968. 2012. View Article : Google Scholar : PubMed/NCBI
7	Wang CH, Kao CH, Chen YF, Wei YH and Tsai TF: Cisd2 mediates lifespan: Is there an interconnection among Ca²⁺ homeostasis, autophagy, and lifespan? Free Radic Res. 48:1–1114. 2014. View Article : Google Scholar : PubMed/NCBI
8	Tsai PH, Chien Y, Chuang JH, Chou SJ, Chien CH, Lai YH, Li HY, Ko YL, Chang YL, Wang CY, et al: Dysregulation of mitochondrial functions and osteogenic differentiation in cisd2-deficient murine induced pluripotent stem cells. Stem Cells Dev. 24:2561–2576. 2015. View Article : Google Scholar : PubMed/NCBI
9	Chang NC, Nguyen M, Bourdon J, Risse PA, Martin J, Danialou G, Rizzuto R, Petrof BJ and Shore GC: Bcl-2-associated autophagy regulator Naf-1 required for maintenance of skeletal muscle. Hum Mol Genet. 21:2277–2287. 2012. View Article : Google Scholar : PubMed/NCBI
10	Chen YF, Kao CH, Chen YT, Wang CH, Wu CY, Tsai CY, Liu FC, Yang CW, Wei YH, Hsu MT, et al: Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice. Genes Dev. 23:1183–1194. 2009. View Article : Google Scholar : PubMed/NCBI
11	Sohn YS, Tamir S, Song L, Michaeli D, Matouk I, Conlan AR, Harir Y, Holt SH, Shulaev V, Paddock ML, et al: NAF-1 and mitoNEET are central to human breast cancer proliferation by maintaining mitochondrial homeostasis and promoting tumor growth. Proc Natl Acad Sci USA. 110:pp. 14676–14681. 2013; View Article : Google Scholar : PubMed/NCBI
12	Liu L, Xia M, Wang J, Zhang W, Zhang Y and He M: CISD2 expression is a novel marker correlating with pelvic lymph node metastasis and prognosis in patients with early-stage cervical cancer. Med Oncol. 31:1832014. View Article : Google Scholar : PubMed/NCBI
13	Wang B, Cai Z, Tao K, Zeng W, Lu F, Yang R, Feng D, Gao G and Yang Q: Essential control of mitochondrial morphology and function by chaperone-mediated autophagy through degradation of PARK7. Autophagy. 12:1215–1228. 2016. View Article : Google Scholar : PubMed/NCBI
14	Wei Y, Pattingre S, Sinha S, Bassik M and Levine B: JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol Cell. 30:678–688. 2008. View Article : Google Scholar : PubMed/NCBI
15	Wang JD, Cao YL, Li Q, Yang YP, Jin M, Chen D, Wang F, Wang GH, Qin ZH, Hu LF and Liu CF: A pivotal role of FOS-mediated BECN1/Beclin 1 upregulation in dopamine D2 and D3 receptor agonist-induced autophagy activation. Autophagy. 11:2057–2073. 2015. View Article : Google Scholar : PubMed/NCBI
16	Choi J, Jung W and Koo JS: Expression of autophagy-related markers beclin-1, light chain 3A, light chain 3B and p62 according to the molecular subtype of breast cancer. Histopathology. 62:275–286. 2013. View Article : Google Scholar : PubMed/NCBI
17	Komatsu M and Ichimura Y: Physiological significance of selective degradation of p62 by autophagy. FEBS Lett. 584:1374–1378. 2010. View Article : Google Scholar : PubMed/NCBI
18	White E: Deconvoluting the context-dependent role for autophagy in cancer. Nat Rev Cancer. 12:401–410. 2012. View Article : Google Scholar : PubMed/NCBI
19	He WS, Dai XF, Jin M, Liu CW and Rent JH: Hypoxia-induced autophagy confers resistance of breast cancer cells to ionizing radiation. Oncol Res. 20:251–258. 2012. View Article : Google Scholar : PubMed/NCBI
20	Mohapatra P, Preet R, Das D, Satapathy SR, Choudhuri T, Wyatt MD and Kundu CN: Quinacrine-mediated autophagy and apoptosis in colon cancer cells is through a p53- and p21-dependent mechanism. Oncol Res. 20:81–91. 2012. View Article : Google Scholar : PubMed/NCBI
21	Sasazawa Y, Sato N, Umezawa K and Simizu S: Conophylline protects cells in cellular models of neurodegenerative diseases by inducing mammalian target of rapamycin (mTOR)-independent autophagy. J Biol Chem. 290:6168–6178. 2015. View Article : Google Scholar : PubMed/NCBI
22	Brassesco MS, Pezuk JA, Morales AG, de Oliveira JC, Valera ET, da Silva GN, de Oliveira HF, Scrideli CA, Umezawa K and Tone LG: Cytostatic in vitro effects of DTCM-glutarimide on bladder carcinoma cells. Asian Pac J Cancer Prev. 13:1957–1962. 2012. View Article : Google Scholar : PubMed/NCBI
23	Allen M, Bjerke M, Edlund H, Nelander S and Westermark B: Origin of the U87MG glioma cell line: Good news and bad news. Sci Transl Med. 8:354re32016. View Article : Google Scholar : PubMed/NCBI
24	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
25	Yuan J, Zhang Y, Sheng Y, Fu X, Cheng H and Zhou R: MYBL2 guides autophagy suppressor VDAC2 in the developing ovary to inhibit autophagy through a complex of VDAC2-BECN1-BCL2L1 in mammals. Autophagy. 11:1081–1098. 2015. View Article : Google Scholar : PubMed/NCBI
26	Carchman EH, Rao J, Loughran PA, Rosengart MR and Zuckerbraun BS: Heme oxygenase-1-mediated autophagy protects against hepatocyte cell death and hepatic injury from infection/sepsis in mice. Hepatology. 53:2053–2062. 2011. View Article : Google Scholar : PubMed/NCBI
27	Wang L, Ouyang F, Liu X, Wu S, Wu HM, Xu Y, Wang B, Zhu J, Xu X and Zhang L: Overexpressed CISD2 has prognostic value in human gastric cancer and promotes gastric cancer cell proliferation and tumorigenesis via AKT signaling pathway. Oncotarget. 7:3791–3805. 2016. View Article : Google Scholar : PubMed/NCBI
28	Chen B, Shen S, Wu J, Hua Y, Kuang M, Li S and Peng B: CISD2 associated with proliferation indicates negative prognosis in patients with hepatocellular carcinoma. Int J Clin Exp Pathol. 8:13725–13738. 2015.PubMed/NCBI
29	Wang P, Liang J, Li Y and Li J, Yang X, Zhang X, Han S, Li S and Li J: Down-regulation of miRNA-30a alleviates cerebral ischemic injury through enhancing beclin 1-mediated autophagy. Neurochem Res. 39:1279–1291. 2014. View Article : Google Scholar : PubMed/NCBI
30	Zhang X, Shi H, Lin S, Ba M and Cui S: MicroRNA-216a enhances the radiosensitivity of pancreatic cancer cells by inhibiting beclin-1-mediated autophagy. Oncol Rep. 34:1557–1564. 2015. View Article : Google Scholar : PubMed/NCBI
31	Nishikawa M, Miyake H, Liu B and Fujisawa M: Expression pattern of autophagy-related markers in non-metastatic clear cell renal cell carcinoma: Association with disease recurrence following radical nephrectomy. J Cancer Res Clin Oncol. 141:1585–1591. 2015. View Article : Google Scholar : PubMed/NCBI
32	Wong AS, Lee RH, Cheung AY, Yeung PK, Chung SK, Cheung ZH and Ip NY: Cdk5-mediated phosphorylation of endophilin B1 is required for induced autophagy in models of Parkinson's disease. Nat Cell Biol. 13:568–579. 2011. View Article : Google Scholar : PubMed/NCBI
33	Wen Z, Shu Y, Gao C, Wang X, Qi G, Zhang P, Li M, Shi J and Tian B: CDK5-mediated phosphorylation and autophagy of RKIP regulate neuronal death in Parkinson's disease. Neurobiol Aging. 35:2870–2880. 2014. View Article : Google Scholar : PubMed/NCBI
34	Wang Y, Shen J, Xiong X, Xu Y, Zhang H, Huang C, Tian Y, Jiao C, Wang X and Li X: Remote ischemic preconditioning protects against liver ischemia-reperfusion injury via heme oxygenase-1-induced autophagy. PLoS One. 9:e988342014. View Article : Google Scholar : PubMed/NCBI