Department of Pathology, College of Basic Medical Sciences and the First Affiliated Hospital, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, 110122, People's Republic of China.
J Exp Clin Cancer Res. 2019 Jan 25;38(1):35. doi: 10.1186/s13046-019-1042-1.
The transcription factor PR domain containing 16 (PRDM16) is known to play a significant role in the determination and function of brown and beige fat. However, the role of PRDM16 in tumor biology has not been well addressed. Here we investigated the impact of PRDM16 on tumor growth and metastasis in lung cancer.
UALCAN database, immunoblotting and immunohistochemistry analysis were used to assess PRDM16 expression in lung cancer patients. Kaplan-Meier plotter database was used to analyze the overall survival of patients with lung cancer stratified by PRDM16 expression. PRDM16 overexpression and knockdown experiments were conducted to assess the effects of PRDM16 on growth and metastasis in vitro and in vivo, and its molecular mechanism was investigated in lung adenocarcinoma cells by chromatin immunoprecipitation-sequencing (ChIP-Seq), real time-quantitative PCR (RT-qPCR), luciferase assay, xenograft models and rescue experiments.
PRDM16 was downregulated in lung adenocarcinomas, and its expression level correlated with key pathological characteristics and prognoses of lung adenocarcinoma patients. Overexpressing PRDM16 inhibited the epithelial-to-mesenchymal transition (EMT) of cancer cells both in vivo and in vitro by repressing the transcription of Mucin-4 (MUC4), one of the regulators of EMT in lung adenocarcinomas. Furthermore, deleting the PR domain from PRDM16 increased the transcriptional repression of MUC4 by exhibiting significant differences in histone modifications on its promoter.
Our findings demonstrate a critical interplay between transcriptional and epigenetic modifications during lung adenocarcinoma progression involving EMT of cancer cells and suggest that PRDM16 is a metastasis suppressor and potential therapeutic target for lung adenocarcinomas.
转录因子 PR 结构域包含 16（PRDM16）已知在棕色和米色脂肪的决定和功能中发挥重要作用。然而，PRDM16 在肿瘤生物学中的作用尚未得到很好的解决。在这里，我们研究了 PRDM16 对肺癌肿瘤生长和转移的影响。
使用 UALCAN 数据库、免疫印迹和免疫组织化学分析评估肺癌患者中 PRDM16 的表达。Kaplan-Meier plotter 数据库用于分析按 PRDM16 表达分层的肺癌患者的总生存率。进行 PRDM16 过表达和敲低实验，以评估 PRDM16 对体外和体内生长和转移的影响，并通过染色质免疫沉淀测序（ChIP-Seq）、实时定量 PCR（RT-qPCR）、荧光素酶测定、异种移植模型和挽救实验研究其在肺腺癌细胞中的分子机制。
PRDM16 在肺腺癌中下调，其表达水平与肺腺癌患者的关键病理特征和预后相关。过表达 PRDM16 通过抑制肺腺癌中 EMT 的一个调节剂 Mucin-4（MUC4）的转录，在体内和体外均抑制癌细胞的上皮-间质转化（EMT）。此外，从 PRDM16 中删除 PR 结构域通过其启动子上的组蛋白修饰表现出对 MUC4 的转录抑制增加，从而产生显著差异。
我们的研究结果表明，在涉及 EMT 的肺腺癌进展过程中，转录和表观遗传修饰之间存在关键相互作用，提示 PRDM16 是肺腺癌的转移抑制因子和潜在治疗靶点。
Zotero 插件
