PRDM16 Inhibits Cell Proliferation and Migration via Epithelial-to-Mesenchymal Transition by Directly Targeting Pyruvate Carboxylase in Papillary Thyroid Cancer.
PRDM16 Inhibits Cell Proliferation and Migration via Epithelial-to-Mesenchymal Transition by Directly Targeting Pyruvate Carboxylase in Papillary Thyroid Cancer.
复制标题
DOI：
10.3389/fcell.2021.723777
复制
发表时间：
2021
影响因子：
5.5
通讯作者：
Ji QH
中科院分区：
文献类型：
--
作者：
Liu WL;Guan Q;Wen D;Ma B;Xu WB;Hu JQ;Wei WJ;Li DS;Wang Y;Xiang J;Liao T;Ji QH
PRDM 16（称为MEL 1）是PR结构域锌指家族的成员，与多种生物学过程有关，包括癌症。目前尚不清楚PRDM 16是否参与甲状腺乳头状癌（PTC）的肿瘤进展。我们通过qRT-PCR鉴定了PTC组织中PRDM 16的表达水平，并分析了其与复旦大学上海肿瘤中心（FUSCC）和TCGA队列中临床特征的关系。我们在体内和体外测试了PRDM 16在PTC细胞中的功能。通过RNA测序、拯救实验、荧光素酶测定和染色质免疫沉淀测定，我们发现了PRDM 16的直接下游靶标丙酮酸羧化酶（PC）。PRDM 16在甲状腺乳头状癌组织中下调，并且在FUSCC和TCGA队列中与淋巴结转移和甲状腺外扩展显著相关。PRDM 16过表达可抑制PTC细胞的增殖和迁移，抑制其上皮细胞向间质细胞的转化。PC在甲状腺乳头状癌组织中表达上调。敲低PC可抑制TPC-1和K1细胞的增殖和迁移。PRDM 16对细胞增殖和迁移的抑制作用是PC依赖性的。PRDM 16可以直接结合PC启动子并在转录水平抑制其表达。此外，PRDM 16和PC的mRNA表达水平在人PTC组织中呈负相关。结论：PRDM 16通过与PC启动子直接结合，在PTC中发挥抗肿瘤作用和EMT抑制作用。PRDM 16可能成为甲状腺乳头状癌治疗的新靶点。
PRDM16 (known as MEL1), a member of the PR domain zinc finger family, has been implicated in multiple biological processes, including cancers. It is not clear yet whether PRDM16 is involved in tumor progress of papillary thyroid cancer (PTC). We identified the PRDM16 expression level in PTC tissues by qRT-PCR and analyzed its relationship with clinical characteristics in both Fudan University Shanghai Cancer Center (FUSCC) and TCGA cohorts. We tested the function of PRDM16 in PTC cells both in vivo and in vitro. We found a direct downstream target of PRDM16, pyruvate carboxylase (PC), by RNA-sequencing, rescue experiments, luciferase assay, and chromatin immunoprecipitation assay. PRDM16 was downregulated in papillary thyroid cancer tissues and was significantly related with lymph node metastases and extrathyroidal extension in both FUSCC and TCGA cohorts. Overexpression of PRDM16 could attenuate proliferation and migration of PTC cells via inhibiting the epithelial-to-mesenchymal transition process. PC was upregulated in papillary thyroid cancer tissues. Knockdown of PC could inhibit proliferation and migration in TPC-1 and K1 cells. The repression effect on cell proliferation and migration from PRDM16 was PC dependent. PRDM16 could directly bind to the PC promoter and inhibit its expression at the transcription level. Moreover, the mRNA expression level of PRDM16 and PC was negatively related in human PTC tissues. In conclusion, PRDM16 exhibited an antitumor effect and EMT inhibition function in PTC by directly binding with the PC promoter. PRDM16 may be a novel therapeutic target in papillary thyroid cancer.
登录
查看更多内容
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
RARRES3通过调节粘附和分化来抑制乳腺癌肺转移。
影响因子：
11.1
作者：
Morales M;Arenas EJ;Urosevic J;Guiu M;Fernández E;Planet E;Fenwick RB;Fernández-Ruiz S;Salvatella X;Reverter D;Carracedo A;Massagué J;Gomis RR
通讯作者：
Gomis RR
影响因子：
20.3
作者：
Mochizuki, N;Shimizu, S;Morishita, K
通讯作者：
Morishita, K
影响因子：
29
作者：
Seale, Patrick;Kajimura, Shingo;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
影响因子：
5.4
作者：
Sapuppo, G.;Palermo, F.;Pellegriti, G.
通讯作者：
Pellegriti, G.