<br>SMYD3 通过 H3K4me3 介导的 PKM2 转录促进弥漫性大 B 细胞淋巴瘤中的有氧糖酵解,Cell Death & Disease

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SMYD3 通过 H3K4me3 介导的 PKM2 转录促进弥漫性大 B 细胞淋巴瘤中的有氧糖酵解
Cell Death & Disease ( IF 8.1 ) Pub Date : 2022-09-03 , DOI: 10.1038/s41419-022-05208-7
Tian Tian _{1,

2,

3} , Jiwei Li _{1,

2,

3} , Di Shi _{1,

2,

3} , Yupeng Zeng _{1,

2,

3} , Baohua Yu _{1,

2,

3} , Xiaoqiu Li _{1,

2,

3} , Ping Wei _{1,

2,

3,

4} , Xiaoyan Zhou _{1,

2,

3}

Affiliation

组蛋白甲基转移酶 (HMT) 的遗传异常经常发生在弥漫性大 B 细胞淋巴瘤 (DLBCL) 中，并且与其进展相关。 SET 和 MYND 结构域包含 3 (SMYD3) 是一种 HMT，在多种肿瘤中表达上调并促进其恶性。然而，据我们所知，迄今为止，SMYD3 在 DLBCL 中的功能尚未得到研究。本研究首先根据现有文献筛选出22个与癌症发生相关的HMT基因，发现SMYD3高表达与DLBCL患者无进展生存期较差显着相关。 SMYD3 蛋白水平上调，与 DLBCL 患者的不良预后和化疗反应不良呈正相关。功能检查表明，SMYD3 在体外和体内增加了 DLBCL 细胞的细胞增殖和有氧糖酵解通量，并在体外降低了细胞对阿霉素的敏感性。此外，SMYD3可以直接结合丙酮酸激酶M2（ PKM2 ）的特定序列，并通过H3K4me3介导的PKM2转录促进DLBCL细胞增殖和有氧糖酵解。临床上，SMYD3的表达与PKM2的表达呈正相关，并且高SMYD3与[(18)F]-氟脱氧葡萄糖((18)F-FDG)PET/计算机断层扫描(PET)检测到的高最大标准化摄取值(SUVmax)显着相关。 /CT）在 DLBCL 样本中。 SMYD3 和 PKM2 的同时表达与 DLBCL 患者的不良无进展生存率和总生存率呈正相关，可能作为 DLBCL 的新型生物标志物。

"点击查看英文标题和摘要"

SMYD3 promotes aerobic glycolysis in diffuse large B-cell lymphoma via H3K4me3-mediated PKM2 transcription

Genetic abnormalities in histone methyltransferases (HMTs) frequently occur in diffuse large B-cell lymphoma (DLBCL) and are related to its progression. SET and MYND domain containing 3 (SMYD3) is an HMT that is upregulated in various tumors and promotes their malignancy. However, to the best of our knowledge, the function of SMYD3 in DLBCL has not been investigated thus far. In the present study, 22 HMT genes related to cancer development were first selected according to current literature, and it was found that high SMYD3 expression was significantly associated with poor progression-free survival in patients with DLBCL. SMYD3 protein levels were upregulated and positively associated with poor prognosis and poor responsiveness to chemotherapy in patients with DLBCL. Functional examinations demonstrated that SMYD3 increased cell proliferation and the flux of aerobic glycolysis in DLBCL cells in vitro and in vivo and decreased cell sensitivity to doxorubicin in vitro. Moreover, SMYD3 could directly bind to specific sequences of Pyruvate Kinase M2 (PKM2) and promote DLBCL cell proliferation and aerobic glycolysis via H3K4me3-mediated PKM2 transcription. Clinically, SMYD3 expression positively correlated with that of PKM2, and high SMYD3 was significantly associated with high maximum standardized uptake value (SUVmax) detected by [(18)F]-fluorodeoxyglucose ((18)F-FDG) PET/computed tomography (PET/CT) in DLBCL samples. Concomitant expression of SMYD3 and PKM2 positively correlated with poor progression-free and overall survival in patients with DLBCL and may serve as novel biomarkers in DLBCL.

更新日期：2022-09-03

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