EHMT2 通过抑制 PI3K/AKT/mTOR 通路促进前列腺癌的发展。
EHMT2 promotes the development of prostate cancer by inhibiting PI3K/AKT/mTOR pathway.
机构信息
Department of Urological Surgery, the Second Affiliated Hospital of Jilin University, Changchun, China.
出版信息
Eur Rev Med Pharmacol Sci. 2019 Sep;23(18):7808-7815. doi: 10.26355/eurrev_201909_18990.
OBJECTIVE
To investigate the expression characteristics and the potential role of euchromatic histone-lysine N-methyltransferase 2 (EHMT2) in the clinical pathology and prognosis of prostate cancer (PCa).
PATIENTS AND METHODS
Quantitative Real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of EHMT2 in 55 pairs of PCa tissues and adjacent normal tissues. The relationship between EHMT2 expression and the pathological features, as well as the prognosis of PCa patients was analyzed. EHMT2 expression in PCa cells was determined by qRT-PCR as well. In addition, EHMT2 knockdown model was constructed by transfection of the small interfering RNA in PCa cell lines PC-3 and DU-145. The regulatory effects of EHMT2 on the behaviors of PCa cells were evaluated through cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU), colony formation assay and flow cytometry. Finally, we detected the protein levels of relative genes in PI3K/AKT/mTOR pathway through Western blot.
RESULTS
QRT-PCR results showed that the expression level of EHMT2 in PCa tissues was markedly higher than that in adjacent normal tissues. Compared with PCa patients with low expression of EHMT2, those with high expression of EHMT2 had higher pathological grade and lower overall survival. EHMT2 was also highly expressed in PCa cell lines. Knockdown of EHMT2 inhibited the proliferative potential and induced apoptosis of PCa cells. Western blot results revealed that PCa cells with EHMT2 knockdown presented downregulated p-PI3K, p-AKT and p-mTOR.
CONCLUSIONS
EHMT2 was highly expressed in PCa, and its expression is closely correlated with tumor stage and poor prognosis of PCa patients. EHMT2 promoted the malignant progression of PCa by inhibiting PI3K/AKT/mTOR pathway.
目的
研究常染色质组蛋白赖氨酸 N-甲基转移酶 2（EHMT2）在前列腺癌（PCa）临床病理及预后中的表达特征及潜在作用。
患者与方法
采用实时定量聚合酶链反应（qRT-PCR）检测 55 对 PCa 组织及相邻正常组织中 EHMT2 的表达，分析 EHMT2 表达与 PCa 患者病理特征及预后的关系。qRT-PCR 检测 PCa 细胞中 EHMT2 的表达。另外，通过转染 PCa 细胞系 PC-3 和 DU-145 的小干扰 RNA 构建 EHMT2 敲低模型。通过细胞计数试剂盒-8（CCK-8）、5-乙炔基-2'-脱氧尿苷（EdU）、集落形成实验和流式细胞术评估 EHMT2 对 PCa 细胞行为的调控作用。最后，通过 Western blot 检测 PI3K/AKT/mTOR 通路中相关基因的蛋白水平。
结果
qRT-PCR 结果显示，EHMT2 在 PCa 组织中的表达水平明显高于相邻正常组织。与 EHMT2 低表达的 PCa 患者相比，EHMT2 高表达的患者病理分级更高，总生存期更低。EHMT2 在 PCa 细胞系中也呈高表达。敲低 EHMT2 抑制了 PCa 细胞的增殖能力并诱导其凋亡。Western blot 结果显示，EHMT2 敲低的 PCa 细胞中 p-PI3K、p-AKT 和 p-mTOR 表达下调。
结论
EHMT2 在 PCa 中呈高表达，其表达与肿瘤分期及 PCa 患者预后密切相关。EHMT2 通过抑制 PI3K/AKT/mTOR 通路促进了 PCa 的恶性进展。
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