MicroRNA-663 inhibits the proliferation, migration and invasion of glioblastoma cells via targeting TGF-β1 Retraction in /10.3892/or.2022.8324

Li,Qizhuang; Cheng,Quan; Chen,Zigui; Peng,Renjun; Chen,Rui; Ma,Zhiming; Wan,Xin; Liu,Jincan; Meng,Ming; Peng,Zhigang; Jiang,Bing

doi:10.3892/or.2015.4432

MicroRNA-663 inhibits the proliferation, migration and invasion of glioblastoma cells via targeting TGF-β1

Retraction in: /10.3892/or.2022.8324

Authors:
- Qizhuang Li
- Quan Cheng
- Zigui Chen
- Renjun Peng
- Rui Chen
- Zhiming Ma
- Xin Wan
- Jincan Liu
- Ming Meng
- Zhigang Peng
- Bing Jiang
View Affiliations

Affiliations: Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan 410078, P.R. China
Published online on: November 17, 2015 https://doi.org/10.3892/or.2015.4432
Pages: 1125-1134

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Cell migration and invasion are key processes involved during tumor metastasis. Recently, microRNAs (miRs) have been demonstrated to play important roles in the regulation of cancer metastasis. However, the underlying mechanisms remain unknown. Here, we aimed to investigate the exact role of miR-663 in the metastasis of glioblastoma as well as the underlying mechanisms. By performing quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis, we demonstrated that miR-663 was significantly downregulated in glioblastoma tissues (n=25), when compared to that in normal brain tissues (n=15). In addition, its expression levels were also reduced in human glioblastoma cell lines, A172 and U87. Furthermore, restoration of miR-663 expression led to a significant decrease in the cell proliferation, migration and invasion of human glioblastoma A172 and U87 cells. We further identified TGF-β1 as a direct target of miR-663, and found that the expression of TGF-β1 was negatively mediated by miR-663 at the post-transcriptional level in glioblastoma cells. Moreover, overexpression of TGF-β1 significantly reversed the inhibitory effects of miR-663 upregulation on the proliferation, migration and invasion in A172 and U87 cells. In addition, our data suggest that MMP2 and E-cadherin, a key factor in epithelial-mesenchymal transition (EMT), are involved in the miR-633/TGF-β1-mediated metastasis of glioblastoma. In summary, miR-663 plays an inhibitory role in the regulation of proliferation, migration and invasion of glioblastoma cells, partly at least, via direct mediation of TGF-β1 as well as downstream MMP2 and E-cadherin. Therefore, we suggest that miR-663 is a potential candidate for the prevention of glioblastoma metastasis.

View Figures

View References

1	Goodenberger ML and Jenkins RB: Geneticss of adult glioma. Cancer Genet. 205:613–621. 2012. View Article : Google Scholar : PubMed/NCBI
2	Brower JV, Clark PA, Lyon W and Kuo JS: MicroRNAs in cancer: Glioblastoma and glioblastoma cancer stem cells. Neurochem Int. 77:68–77. 2014. View Article : Google Scholar : PubMed/NCBI
3	Cancer Genome Atlas Research Network: Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 455:1061–1068. 2008. View Article : Google Scholar : PubMed/NCBI
4	Marumoto T and Saya H: Molecular biology of glioma. Adv Exp Med Biol. 746:2–11. 2012. View Article : Google Scholar : PubMed/NCBI
5	Treiber T, Treiber N and Meister G: Regulation of microRNA biogenesis and function. Thromb Haemost. 107:605–610. 2012. View Article : Google Scholar : PubMed/NCBI
6	Fabbri M, Calore F, Paone A, Galli R and Calin GA: Epigenetic regulation of miRNAs in cancer. Adv Exp Med Biol. 754:137–148. 2013. View Article : Google Scholar
7	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
8	Hermansen SK and Kristensen BW: MicroRNA biomarkers in glioblastoma. J Neurooncol. 114:13–23. 2013. View Article : Google Scholar : PubMed/NCBI
9	Lehmann U, Hasemeier B, Römermann D, Müller M, Länger F and Kreipe H: Epigenetic inactivation of microRNA genes in mammary carcinoma. Verh Dtsch Ges Pathol. 91:214–220. 2007.In German.
10	Tili E, Michaille JJ, Adair B, Alder H, Limagne E, Taccioli C, Ferracin M, Delmas D, Latruffe N and Croce CM: Resveratrol decreases the levels of miR-155 by upregulating miR-663, a microRNA targeting JunB and JunD. Carcinogenesis. 31:1561–1566. 2010. View Article : Google Scholar : PubMed/NCBI
11	Zhang Y, Zhou X, Xu X, Zhang M, Wang X, Bai X, Li H, Kan L, Zhou Y, Niu H, et al: Waltonitone induces apoptosis through mir-663-induced Bcl-2 downregulation in non-small cell lung cancer. Tumour Biol. 36:871–876. 2015. View Article : Google Scholar
12	Pan J, Hu H, Zhou Z, Sun L, Peng L, Yu L, Sun L, Liu J, Yang Z and Ran Y: Tumor-suppressive mir-663 gene induces mitotic catastrophe growth arrest in human gastric cancer cells. Oncol Rep. 24:105–112. 2010.PubMed/NCBI
13	Liu ZY, Zhang GL, Wang MM, Xiong YN and Cui HQ: MicroRNA-663 targets TGFB1 and regulates lung cancer proliferation. Asian Pac J Cancer Prev. 12:2819–2823. 2011.PubMed/NCBI
14	Shi Y, Chen C, Zhang X, Liu Q, Xu JL, Zhang HR, Yao XH, Jiang T, He ZC, Ren Y, et al: Primate-specific miR-663 functions as a tumor suppressor by targeting PIK3CD and predicts the prognosis of human glioblastoma. Clin Cancer Res. 20:1803–1813. 2014. View Article : Google Scholar : PubMed/NCBI
15	Shi Y, Chen C, Yu SZ, Liu Q, Rao J, Zhang HR, Xiao HL, Fu TW, Long H, He ZC, et al: miR-663 suppresses oncogenic function of CXCR4 in glioblastoma. Clin Cancer Res. 21:4004–4013. 2015. View Article : Google Scholar : PubMed/NCBI
16	Zhao L and Hantash BM: TGF-β1 regulates differentiation of bone marrow mesenchymal stem cells. Vitam Horm. 87:127–141. 2011. View Article : Google Scholar
17	Perera M, Tsang CS, Distel RJ, Lacy JN, Ohno-Machado L, Ricchiuti V, Samaranayake LP, Smejkal GB, Smith MG, Trachtenberg AJ, et al: TGF-beta1 interactome: Metastasis and beyond. Cancer Genomics Proteomics. 7:217–229. 2010.PubMed/NCBI
18	Caraci F, Battaglia G, Bruno V, Bosco P, Carbonaro V, Giuffrida ML, Drago F, Sortino MA, Nicoletti F and Copani A: TGF-β1 pathway as a new target for neuroprotection in Alzheimer's disease. CNS Neurosci Ther. 17:237–249. 2011. View Article : Google Scholar
19	Liu YN, Zha WJ, Ma Y, Chen FF, Zhu W, Ge A, Zeng XN and Huang M: Galangin attenuates airway remodelling by inhibiting TGF-β1-mediated ROS generation and MAPK/Akt phosphorylation in asthma. Sci Rep. 5:117582015. View Article : Google Scholar
20	Chen W, Zhong X, Wei Y, Liu Y, Yi Q, Zhang G, He L, Chen F, Liu Y and Luo J: TGF-β regulates survivin to affect cell cycle and the expression of EGFR and MMP9 in glioblastoma. Mol Neurobiol. Feb 17–2015.(Epub ahead of print) http://dx.doi.org/10.1007/s12035-015-9121-6. View Article : Google Scholar
21	Joseph JV, Conroy S, Tomar T, Eggens-Meijer E, Bhat K, Copray S, Walenkamp AM, Boddeke E, Balasubramanyian V, Wagemakers M, et al: TGF-β is an inducer of ZEB1-dependent mesenchymal transdifferentiation in glioblastoma that is associated with tumor invasion. Cell Death Dis. 5:e14432014. View Article : Google Scholar
22	Liu Z, Long X, Chao C, Yan C, Wu Q, Hua S, Zhang Y, Wu A and Fang W: Knocking down CDK4 mediates the elevation of let-7c suppressing cell growth in nasopharyngeal carcinoma. BMC Cancer. 14:2742014. View Article : Google Scholar : PubMed/NCBI
23	Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI
24	Lv S, Sun B, Dai C, Shi R, Zhou X, Lv W, Zhong X, Wang R and Ma W: The downregulation of microRNA-146a modulates TGF-β signaling pathways activity in glioblastoma. Mol Neurobiol. 52:1257–1262. 2015. View Article : Google Scholar
25	Yao Y, Ma J, Xue Y, Wang P, Li Z, Li Z, Hu Y, Shang X and Liu Y: miR-449a exerts tumor-suppressive functions in human glioblastoma by targeting Myc-associated zinc-finger protein. Mol Oncol. 9:640–656. 2015. View Article : Google Scholar
26	Yu JM, Sun W, Hua F, Xie J, Lin H, Zhou DD and Hu ZW: BCL6 induces EMT by promoting the ZEB1-mediated transcription repression of E-cadherin in breast cancer cells. Cancer Lett. 365:190–200. 2015. View Article : Google Scholar : PubMed/NCBI
27	Wang Z, Wang B, Shi Y, Xu C, Xiao HL, Ma LN, Xu SL, Yang L, Wang QL, Dang WQ, et al: Oncogenic miR-20a and miR-106a enhance the invasiveness of human glioma stem cells by directly targeting TIMP-2. Oncogene. 34:1407–1419. 2015. View Article : Google Scholar
28	Tivnan A and McDonald KL: Current progress for the use of miRNAs in glioblastoma treatment. Mol Neurobiol. 48:757–768. 2013. View Article : Google Scholar : PubMed/NCBI
29	Zhao S, Liu H, Liu Y, Wu J, Wang C, Hou X, Chen X, Yang G, Zhao L, Che H, et al: miR-143 inhibits glycolysis and depletes stemness of glioblastoma stem-like cells. Cancer Lett. 333:253–260. 2013. View Article : Google Scholar : PubMed/NCBI
30	Xiao S, Yang Z, Lv R, Zhao J, Wu M, Liao Y and Liu Q: miR-135b contributes to the radioresistance by targeting GSK3β in human glioblastoma multiforme cells. PLoS One. 9:e1088102014. View Article : Google Scholar
31	Xu F, Li F, Zhang W and Jia P: Growth of glioblastoma is inhibited by miR-133-mediated EGFR suppression. Tumour Biol. Jul 3–2015.Epub ahead of print. View Article : Google Scholar
32	Jiang Y, Yin L, Jing H and Zhang H: MicroRNA-219-5p exerts tumor suppressor function by targeting ROBO1 in glioblastoma. Tumour Biol. Jun 17–2015.Epub ahead of print. View Article : Google Scholar
33	Huang BS, Luo QZ, Han Y, Li XB, Cao LJ and Wu LX: micro-RNA-223 promotes the growth and invasion of glioblastoma cells by targeting tumor suppressor PAX6. Oncol Rep. 30:2263–2269. 2013.PubMed/NCBI
34	Xu J, Xu W and Zhu J: Propofol suppresses proliferation and invasion of glioma cells by upregulating microRNA-218 expression. Mol Med Rep. 12:4815–4820. 2015.PubMed/NCBI
35	Shi L, Fei X, Wang Z and You Y: PI3K inhibitor combined with miR-125b inhibitor sensitize TMZ-induced anti-glioma stem cancer effects through inactivation of Wnt/β-catenin signaling pathway. In Vitro Cell Dev Biol Anim. Jul 14–2015.Epub ahead of print. View Article : Google Scholar
36	Scarpa S, Coppa A, Ragano-Caracciolo M, Mincione G, Giuffrida A, Modesti A and Colletta G: Transforming growth factor beta regulates differentiation and proliferation of human neuroblastoma. Exp Cell Res. 229:147–154. 1996. View Article : Google Scholar : PubMed/NCBI
37	Wang J, Li Y, Wang X and Jiang C: Ursolic acid inhibits proliferation and induces apoptosis in human glioblastoma cell lines U251 by suppressing TGF-β1/miR-21/PDCD4 pathway. Basic Clin Pharmacol Toxicol. 111:106–112. 2012.PubMed/NCBI
38	Hu W, Xu S, Yao B, Hong M, Wu X, Pei H, Chang L, Ding N, Gao X, Ye C, et al: miR-663 inhibits radiation-induced bystander effects by targeting TGFB1 in a feedback mode. RNA Biol. 11:1189–1198. 2014. View Article : Google Scholar : PubMed/NCBI
39	Hong Q, Yu S, Geng X, Duan L, Zheng W, Fan M, Chen X and Wu D: High concentrations of uric acid inhibit endothelial cell migration via miR-663 which regulates phosphatase and tensin homolog by targeting transforming growth factor-β1. Microcirculation. 22:306–314. 2015. View Article : Google Scholar : PubMed/NCBI
40	Liu L, Dai Q, Min Z and Zhang M: Transforming growth factor β1 enhances the invasiveness of human glioma cell line via ERK/MAPK pathway. Nan Fang Yi Ke Da Xue Xue Bao. 33:1744–1747. 2013.In Chinese. PubMed/NCBI
41	Li W, Kidiyoor A, Hu Y, Guo C, Liu M, Yao X, Zhang Y, Peng B and Zheng J: Evaluation of transforming growth factor-β1 suppress Pokemon/epithelial-mesenchymal transition expression in human bladder cancer cells. Tumour Biol. 36:1155–1162. 2015. View Article : Google Scholar : PubMed/NCBI