SET and MYND domain-containing protein 3 is overexpressed in human glioma and contributes to tumorigenicity Retraction in /10.3892/or.2024.8825

Dai,Bin; Wan,Weiqing; Zhang,Peng; Zhang,Yisong; Pan,Changcun; Meng,Guolu; Xiao,Xinru; Wu,Zhen; Jia,Wang; Zhang,Junting; Zhang,Liwei

doi:10.3892/or.2015.4239

SET and MYND domain-containing protein 3 is overexpressed in human glioma and contributes to tumorigenicity

Retraction in: /10.3892/or.2024.8825

Authors:
- Bin Dai
- Weiqing Wan
- Peng Zhang
- Yisong Zhang
- Changcun Pan
- Guolu Meng
- Xinru Xiao
- Zhen Wu
- Wang Jia
- Junting Zhang
- Liwei Zhang
View Affiliations

Affiliations: Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Beijing 100050, P.R. China
Published online on: September 1, 2015 https://doi.org/10.3892/or.2015.4239
Pages: 2722-2730

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

SET and MYND domain-containing protein 3 (SMYD3) is a histone H3 lysine 4 (H3K4) di- and tri-methyltransferase that forms a transcriptional complex with RNA polymerase II and plays an important role in early embryonic lineage commitment through the activation of lineage-specific genes. SMYD3 activates the transcription of oncogenes and cell cycle genes in gastric and breast cancer cells. However, the contribution of SMYD3 in glioma tumorigenesis remains unknown. Here, we determined the expression of SMYD3 and assessed its clinical significance in human glioma. We found that SMYD3 was overexpressed in human glioma but not in normal brain tissue. The level of SMYD3 protein expression in human glioma tissues was directly correlated with the glioma grade. The level of SMYD3 protein expression in human glioma tissues was inversely correlated with patient survival. Enforced SMYD3 expression promoted glioma LN-18 cell proliferation. Inhibition of SMYD3 expression in glioma T98G cells suppressed their anchorage‑independent growth in vitro and tumorigenicity in vivo. Furthermore, we found that SMYD3 regulated the expression of p53 protein, which is essential in SMYD3‑induced cell growth in glioma cells. These results showed that SMYD3 is overexpressed in human glioma and contributes to glioma tumorigenicity through p53. Therefore, SMYD3 may be a new potential therapeutic target for human malignant glioma.

View Figures

View References

1	Cloughesy TF, Cavenee WK and Mischel PS: Glioblastoma: From molecular pathology to targeted treatment. Annu Rev Pathol. 9:1–25. 2014. View Article : Google Scholar
2	DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, Alteri R, Robbins AS and Jemal A: Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 64:252–271. 2014. View Article : Google Scholar : PubMed/NCBI
3	Annibali D, Whitfield JR, Favuzzi E, Jauset T, Serrano E, Cuartas I, Redondo-Campos S, Folch G, Gonzàlez-Juncà A, Sodir NM, et al: Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis. Nat Commun. 5:46322014. View Article : Google Scholar : PubMed/NCBI
4	Ahmed R, Oborski MJ, Hwang M, Lieberman FS and Mountz JM: Malignant gliomas: Current perspectives in diagnosis, treatment, and early response assessment using advanced quantitative imaging methods. Cancer Manag Res. 6:149–170. 2014.PubMed/NCBI
5	Martin C and Zhang Y: Mechanisms of epigenetic inheritance. Curr Opin Cell Biol. 19:266–272. 2007. View Article : Google Scholar : PubMed/NCBI
6	Zhou VW, Goren A and Bernstein BE: Charting histone modifications and the functional organization of mammalian genomes. Nat Rev Genet. 12:7–18. 2011. View Article : Google Scholar
7	Van Aller GS, Reynoird N, Barbash O, Huddleston M, Liu S, Zmoos AF, McDevitt P, Sinnamon R, Le B, Mas G, et al: Smyd3 regulates cancer cell phenotypes and catalyzes histone H4 lysine 5 methylation. Epigenetics. 7:340–343. 2012. View Article : Google Scholar : PubMed/NCBI
8	Cock-Rada AM, Medjkane S, Janski N, Yousfi N, Perichon M, Chaussepied M, Chluba J, Langsley G and Weitzman JB: SMYD3 promotes cancer invasion by epigenetic upregulation of the metalloproteinase MMP-9. Cancer Res. 72:810–820. 2012. View Article : Google Scholar :
9	He C, Xu J, Zhang J, Xie D, Ye H, Xiao Z, Cai M, Xu K, Zeng Y, Li H, et al: High expression of trimethylated histone H3 lysine 4 is associated with poor prognosis in hepatocellular carcinoma. Hum Pathol. 43:1425–1435. 2012. View Article : Google Scholar : PubMed/NCBI
10	Liu L, Kimball S, Liu H, Holowatyj A and Yang ZQ: Genetic alterations of histone lysine methyltransferases and their significance in breast cancer. Oncotarget. 6:2466–2482. 2015. View Article : Google Scholar :
11	Liu Y, Deng J, Luo X, Pan Y, Zhang L, Zhang R and Liang H: Overexpression of SMYD3 was associated with increased STAT3 activation in gastric cancer. Med Oncol. 32:4042015. View Article : Google Scholar
12	Luo XG, Xi T, Guo S, Liu ZP, Wang N, Jiang Y and Zhang TC: Effects of SMYD3 overexpression on transformation, serum dependence, and apoptosis sensitivity in NIH3T3 cells. IUBMB Life. 61:679–684. 2009. View Article : Google Scholar : PubMed/NCBI
13	Xu LX, Li ZH, Tao YF, Li RH, Fang F, Zhao H, Li G, Li YH, Wang J, Feng X, et al: Histone acetyltransferase inhibitor II induces apoptosis in glioma cell lines via the p53 signaling pathway. J Exp Clin Cancer Res. 33:1082014. View Article : Google Scholar : PubMed/NCBI
14	Cohen AL and Colman H: Glioma biology and molecular markers. Cancer Treat Res. 163:15–30. 2015. View Article : Google Scholar
15	Chuikov S, Kurash JK, Wilson JR, Xiao B, Justin N, Ivanov GS, McKinney K, Tempst P, Prives C, Gamblin SJ, et al: Regulation of p53 activity through lysine methylation. Nature. 432:353–360. 2004. View Article : Google Scholar : PubMed/NCBI
16	Huang J, Perez-Burgos L, Placek BJ, Sengupta R, Richter M, Dorsey JA, Kubicek S, Opravil S, Jenuwein T and Berger SL: repression of p53 activity by Smyd2-mediated methylation. Nature. 444:629–632. 2006. View Article : Google Scholar : PubMed/NCBI
17	Wang q, Wang Y, Zhang Y, Zhang Y and Xiao W: The role of uPAR in epithelial-mesenchymal transition in small airway epithelium of patients with chronic obstructive pulmonary disease. Respir Res. 14:672013. View Article : Google Scholar : PubMed/NCBI
18	Sun Y, Wang Y, Fan C, Gao P, Wang X, Wei G and Wei J: Estrogen promotes stemness and invasiveness of ER-positive breast cancer cells through Gli1 activation. Mol Cancer. 13:1372014. View Article : Google Scholar : PubMed/NCBI
19	Wang Y, Wen M, Kwon Y, Xu Y, Liu Y, Zhang P, He X, Wang Q, Huang Y, Jen KY, et al: CUL4A induces epithelial-mesenchymal transition and promotes cancer metastasis by regulating ZEB1 expression. Cancer Res. 74:520–531. 2014. View Article : Google Scholar :
20	Zheng H, Ying H, Yan H, Kimmelman AC, Hiller DJ, Chen AJ, Perry SR, Tonon G, Chu GC, Ding Z, et al: p53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation. Nature. 455:1129–1133. 2008. View Article : Google Scholar : PubMed/NCBI
21	Wang SZ, Luo XG, Shen J, Zou JN, Lu YH and Xi T: Knockdown of SMYD3 by RNA interference inhibits cervical carcinoma cell growth and invasion in vitro. BMB Rep. 41:294–299. 2008. View Article : Google Scholar : PubMed/NCBI
22	Sponziello M, Durante C, Boichard A, Dima M, Puppin C, Verrienti A, Tamburrano G, Di Rocco G, Redler A, Lacroix L, et al: Epigenetic-related gene expression profile in medullary thyroid cancer revealed the overexpression of the histone methyltransferases EZH2 and SMYD3 in aggressive tumours. Mol Cell Endocrinol. 392:8–13. 2014. View Article : Google Scholar : PubMed/NCBI
23	Liu Y, Liu H, Luo X, Deng J, Pan Y and Liang H: Overexpression of SMYD3 and matrix metalloproteinase-9 are associated with poor prognosis of patients with gastric cancer. Tumour Biol. Jan 28–2015.Epub ahead of print. View Article : Google Scholar
24	Suzuki S, Nozawa Y, Tsukamoto S, Kaneko T, Imai H and Minami N: Histone methyltransferase Smyd3 regulates early embryonic lineage commitment in mice. Reproduction. 150:21–30. 2015. View Article : Google Scholar : PubMed/NCBI
25	Hamamoto R, Silva FP, Tsuge M, Nishidate T, Katagiri T, Nakamura Y and Furukawa Y: Enhanced SMYD3 expression is essential for the growth of breast cancer cells. Cancer Sci. 97:113–118. 2006. View Article : Google Scholar : PubMed/NCBI
26	Ren TN, Wang JS, He YM, Xu CL, Wang SZ and Xi T: Effects of SMYD3 over-expression on cell cycle acceleration and cell proliferation in MDA-MB-231 human breast cancer cells. Med Oncol. 28(Suppl 1): S91–S98. 2011. View Article : Google Scholar
27	Liu Y, Luo X, Deng J, Pan Y, Zhang L and Liang H: SMYD3 overexpression was a risk factor in the biological behavior and prognosis of gastric carcinoma. Tumour Biol. 36:2685–2694. 2015. View Article : Google Scholar
28	Xu Y, Wang Y, Ma G, Wang Q and Wei G: CUL4A is overexpressed in human pituitary adenomas and regulates pituitary tumor cell proliferation. J Neurooncol. 116:625–632. 2014. View Article : Google Scholar : PubMed/NCBI
29	Wang Y, Ma G, Wang Q, Wen M, Xu Y, He X, Zhang P, Wang Y, Yang T, Zhan P, et al: Involvement of CUL4A in regulation of multidrug resistance to P-gp substrate drugs in breast cancer cells. Molecules. 19:159–176. 2013. View Article : Google Scholar : PubMed/NCBI