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PAFAH1B2 是 HIF1a 的靶基因,可促进胰腺癌转移。

PAFAH1B2 is a HIF1a target gene and promotes metastasis in pancreatic cancer.

机构信息

Department of General Surgery, Fourth Affiliated Hospital, Hebei Medical University, Shijiazhuang, Hebei, China.

Department of Oncology, The First Hospital of Shijiazhuang, Shijiazhuang, Hebei, China.

出版信息

Biochem Biophys Res Commun. 2018 Jun 27;501(3):654-660. doi: 10.1016/j.bbrc.2018.05.039. Epub 2018 May 16.

DOI:10.1016/j.bbrc.2018.05.039
PMID:29758199
Abstract

Platelet-activating factor acetylhydrolase IB subunit beta (PAFAH1B2) plays important roles in inflammation and anaphylaxis. However, its primary function in pancreatic cancer remains unclear. In the current study, we report that PAFAH1B2 is overexpressed in pancreatic ductal adenocarcinoma (PDAC) and correlated inversely with patient survival. PAFAH1B2 overexpression induced epithelial-mesenchymal transition (EMT), migration and invasion in vitro and metastasis in vivo. Conversely, silencing PAFAH1B2 inhibited these aggressive phenotypes. Moreover, PAFAH1B2 overexpression in PDAC cells was directly mediated by HIF1a. PAFAH1B2 expression in PDAC clinical specimens correlated positively with HIF1a expression. Overall, our results defined PAFAH1B2 as a target gene of HIF1a and a critical driver of PDAC metastatic behaviors.

摘要

血小板激活因子乙酰水解酶 IB 亚基 β(PAFAH1B2)在炎症和过敏反应中发挥重要作用。然而,其在胰腺癌中的主要功能尚不清楚。在本研究中,我们报告 PAFAH1B2 在胰腺导管腺癌(PDAC)中过表达,并与患者生存呈负相关。PAFAH1B2 过表达诱导上皮-间充质转化(EMT)、体外迁移和侵袭以及体内转移。相反,沉默 PAFAH1B2 抑制了这些侵袭表型。此外,PDAC 细胞中 PAFAH1B2 的过表达直接由 HIF1a 介导。PDAC 临床标本中 PAFAH1B2 的表达与 HIF1a 的表达呈正相关。总的来说,我们的研究结果将 PAFAH1B2 定义为 HIF1a 的靶基因和 PDAC 转移行为的关键驱动因子。

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