SET and MYND domain-containing protein 3 is overexpressed in human glioma and contributes to tumorigenicity.
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.
Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Beijing 100050, P.R. China.
Bin
B
Dai
Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Beijing 100050, P.R. China.
Weiqing
W
Wan
Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Beijing 100050, P.R. China.
Peng
P
Zhang
Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Beijing 100050, P.R. China.
Yisong
Y
Zhang
Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Beijing 100050, P.R. China.
Changcun
C
Pan
Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Beijing 100050, P.R. China.
Guolu
G
Meng
Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Beijing 100050, P.R. China.
Xinru
X
Xiao
Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Beijing 100050, P.R. China.
Zhen
Z
Wu
Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Beijing 100050, P.R. China.
Wang
W
Jia
Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Beijing 100050, P.R. China.
Junting
J
Zhang
Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Beijing 100050, P.R. China.
Liwei
L
Zhang
D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D011495:Histone-Lysine N-Methyltransferase; C506278:SMYD3 protein, human