Enhancer of zeste homolog 2 silencing inhibits tumor growth and lung metastasis in osteosarcoma.
The enhancer of zeste homolog 2 (EZH2) methyltransferase is the catalytic subunit of polycomb repressive complex 2 (PRC2), which acts as a transcription repressor via the trimethylation of lysine 27 of histone 3 (H3K27me3). EZH2 has been recognised as an oncogene in several types of tumors; however, its role in osteosarcoma has not been fully elucidated. Herein, we show that EZH2 silencing inhibits tumor growth and lung metastasis in osteosarcoma by facilitating re-expression of the imprinting gene tumor-suppressing STF cDNA 3 (TSSC3). Our previous study showed that TSSC3 acts as a tumor suppressor in osteosarcoma. In this study, we found that EZH2 was abnormally elevated in osteosarcoma, and its overexpression was associated with poor prognosis in osteosarcoma. Silencing of EZH2 resulted in tumor growth inhibition, apoptosis and chemosensitivity enhancement. Moreover, suppression of EZH2 markedly inhibited tumor growth and lung metastasis in vivo. Furthermore, EZH2 knockdown facilitated the re-expression of TSSC3 by reducing H3K27me3 in the promoter region. Cotransfection with siEZH2 and siTSSC3 could partially reverse the ability of siEZH2 alone. We have demonstrated that EZH2 plays a crucial role in tumor growth and distant metastasis in osteosarcoma; its oncogenic role is related to its regulation of the expression of TSSC3.
Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, People's Republic of China.
Yang-Fan
YF
Lv
Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, People's Republic of China.
Guang-Ning
GN
Yan
Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, People's Republic of China.
Gang
G
Meng
Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, People's Republic of China.
Xi
X
Zhang
Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, People's Republic of China.
Qiao-Nan
QN
Guo
D000328:Adult; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002648:Child; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary*; D008297:Male; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D012516:Osteosarcoma / Q000473:pathology*; D063151:Polycomb Repressive Complex 2 / Q000235:genetics*; D055815:Young Adult
C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2