MicroRNA-610 suppresses the proliferation of human glioblastoma cells by repressing CCND2 and AKT3

Mo,Xiaomei; Cao,Qian; Liang,Hui; Liu,Jianmin; Li,Huahui; Liu,Fenghai

doi:10.3892/mmr.2016.4760

MicroRNA-610 suppresses the proliferation of human glioblastoma cells by repressing CCND2 and AKT3

Authors:
- Xiaomei Mo
- Qian Cao
- Hui Liang
- Jianmin Liu
- Huahui Li
- Fenghai Liu
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Affiliations: Department of Pharmacy, Qingdao Women and Children Hospital, Qingdao, Shandong 266034, P.R. China, Heart Center, Qingdao Women and Children Hospital, Qingdao, Shandong 266034, P.R. China, Department of Hematology, Qingdao Women and Children Hospital, Qingdao, Shandong 266034, P.R. China, Department of Neurosurgery, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China, Department of Laboratory Medicine of Qingdao Municipal Hospital, Qingdao, Shandong 266011, P.R. China
Published online on: January 12, 2016 https://doi.org/10.3892/mmr.2016.4760
Pages: 1961-1966
Copyright: © Mo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Previous studies have shown that microRNA (miR)-610 is crucial in a variety of biological processes in various types of human cancer cells. However, the role of this microRNA in glioblastoma (GBM) is presently unclear. In this study, the role of miR‑610 in cell proliferation was investigated in GBM. It was demonstrated that miR‑610 expression is markedly downregulated in GBM cells and GBM tissues compared with normal human astrocytes (NHAs) and normal brain tissue, respectively. Ectopic expression of miR‑610 reduced the proliferation and anchorage‑independent growth of GBM cells, whereas inhibition of miR‑610 promoted this effect. Bioinformatics analysis further revealed cyclin D2 (CCND2) and AKT3, putative tumor promoters, as potential targets of miR‑610. Data from reporter assays showed that miR‑610 directly binds to the 3'‑untranslated region of CCND2 and AKT3 mRNA, and represses their expression at the transcriptional and translational levels. In conclusion, the data provide compelling evidence that miR‑610 functions as an anti‑onco‑miRNA, which is important in inhibiting cell proliferation in GBM, and its anti‑oncogenic effects are mediated chiefly through direct suppression of CCND2 and AKT3 expression.

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1	Wen PY and Kesari S: Malignant gliomas in adults. N Engl J Med. 359:492–507. 2008. View Article : Google Scholar : PubMed/NCBI
2	Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, et al: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 352:987–996. 2005. View Article : Google Scholar : PubMed/NCBI
3	Baek D, Villén J, Shin C, Camargo FD, Gygi SP and Bartel DP: The impact of microRNAs on protein output. Nature. 455:64–71. 2008. View Article : Google Scholar : PubMed/NCBI
4	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
5	Miska EA: How microRNAs control cell division, differentiation and death. Curr Opin Genet Dev. 15:563–568. 2005. View Article : Google Scholar : PubMed/NCBI
6	Cristiano BE, Chan JC, Hannan KM, Lundie NA, Marmy-Conus NJ, Campbell IG, Phillips WA, Robbie M, Hannan RD and Pearson RB: A specific role for AKT3 in the genesis of ovarian cancer through modulation of G(2)-M phase transition. Cancer Res. 66:11718–11725. 2006. View Article : Google Scholar : PubMed/NCBI
7	Koyama-Nasu R, Nasu-Nishimura Y, Todo T, Ino Y, Saito N, Aburatani H, Funato K, Echizen K, Sugano H, Haruta R, et al: The critical role of cyclin D2 in cell cycle progression and tumor-igenicity of glioblastoma stem cells. Oncogene. 32:3840–3845. 2013. View Article : Google Scholar
8	Takai H, Masuda K, Sato T, Sakaguchi Y, Suzuki T, Suzuki T, Koyama-Nasu R, Nasu-Nishimura Y, Katou Y, Ogawa H, et al: 5-Hydroxymethylcytosine plays a critical role in glioblastoma-genesis by recruiting the CHTOP-methylosome complex. Cell Rep. 9:48–60. 2014. View Article : Google Scholar : PubMed/NCBI
9	Li S, Chen T, Zhong Z, Wang Y, Li Y and Zhao X: microRNA-155 silencing inhibits proliferation and migration and induces apoptosis by upregulating BACH1 in renal cancer cells. Mol Med Rep. 5:949–954. 2012.PubMed/NCBI
10	Chang CC, Lin BR, Wu TS, Jeng YM and Kuo ML: Input of microenvironmental regulation on colorectal cancer: Role of the CCN family. World J Gastroenterol. 20:6826–6831. 2014. View Article : Google Scholar : PubMed/NCBI
11	Formosa A, Markert EK, Lena AM, Italiano D, Finazzi-Agro' E, Levine AJ, Bernardini S, Garabadgiu AV, Melino G and Candi E: MicroRNAs, miR-154, miR-299-5p, miR-376a, miR-376c, miR-377, miR-381, miR-487b, miR-485-3p, miR-495 and miR-654-3p, mapped to the 14q32.31 locus, regulate proliferation, apoptosis, migration and invasion in metastatic prostate cancer cells. Oncogene. 30:5173–5182. 2014. View Article : Google Scholar
12	Lehmann U, Streichert T, Otto B, Albat C, Hasemeier B, Christgen H, Schipper E, Hille U, Kreipe HH and Länger F: Identification of differentially expressed microRNAs in human male breast cancer. BMC Cancer. 10:1092010. View Article : Google Scholar : PubMed/NCBI
13	Jin J, Li C, You J and Zhang B: miR-610 suppresses lung cancer cell proliferation and invasion by targeting GJA3. Zhonghua Zhong Liu Za Zhi. 36:405–411. 2014.In Chinese. PubMed/NCBI
14	Wang J, Zhang J, Wu J, Luo D, Su K, Shi W, Liu J, Tian Y and Wei L: MicroRNA-610 inhibits the migration and invasion of gastric cancer cells by suppressing the expression of vaso-dilator-stimulated phosphoprotein. Eur J Cancer. 48:1904–1913. 2012. View Article : Google Scholar
15	Beltran AL, Ordonez JL, Otero AP, Blanca A, Sevillano V, Sanchez-Carbayo M, Kirkali Z, Cheng L, Montironi R, Prieto R and De Alava E: Fluorescence in situ hybridization analysis of CCND3 gene as marker of progression in bladder carcinoma. J Biol Regul Homeost Agents. 27:559–567. 2013.PubMed/NCBI
16	Soung YH, Lee JW, Nam SW, Lee JY, Yoo NJ and Lee SH: Mutational analysis of AKT1, AKT2 and AKT3 genes in common human carcinomas. Oncology. 70:285–289. 2006. View Article : Google Scholar : PubMed/NCBI
17	Agarwal E, Brattain MG and Chowdhury S: Cell survival and metastasis regulation by Akt signaling in colorectal cancer. Cell Signal. 25:1711–1719. 2013. View Article : Google Scholar : PubMed/NCBI
18	Paul-Samojedny M, Suchanek R, Borkowska P, Pudełko A, Owczarek A, Kowalczyk M, Machnik G, Fila-Daniłow A and Kowalski J: Knockdown of AKT3 (PKBγ) and PI3KCA suppresses cell viability and proliferation and induces the apoptosis of glioblastoma multiforme T98G cells. Biomed Res Int. 2014:7681812014. View Article : Google Scholar
19	Parry PV and Engh JA: The role of cyclin-d2 in the tumorgenesis of glioblastoma. Neurosurgery. 71:N22–N23. 2012. View Article : Google Scholar : PubMed/NCBI
20	Guo Y, Yan K, Fang J, Qu Q, Zhou M and Chen F: Let-7b expression determines response to chemotherapy through the regulation of cyclin D1 in glioblastoma. J Exp Clin Cancer Res. 32:412013. View Article : Google Scholar : PubMed/NCBI
21	Terada Y, Inoshita S, Nakashima O, Kuwahara M, Sasaki S and Marumo F: Cyclins and the cyclin-kinase system-their potential roles in nephrology. Nephrol Dial Transplant. 13:1913–1916. 1998. View Article : Google Scholar : PubMed/NCBI
22	Féliers D, Frank MA and Riley DJ: Activation of cyclin D1-Cdk4 and Cdk4-directed phosphorylation of RB protein in diabetic mesangial hypertrophy. Diabetes. 51:3290–3299. 2002. View Article : Google Scholar : PubMed/NCBI
23	Roy SK, Srivastava RK and Shankar S: Inhibition of PI3K/AKT and MAPK/ERK pathways causes activation of FOXO transcription factor, leading to cell cycle arrest and apoptosis in pancreatic cancer. J Mol Signal. 5:102010. View Article : Google Scholar : PubMed/NCBI