Zhejiang Cancer Institute, Cancer Hospital of the University of Chinese Academy of Sciences; Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, China.
Department of anaesthesiology, Cancer Hospital of the University of Chinese Academy of Sciences; Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, China.
J Clin Lab Anal. 2022 Sep;36(9):e24617. doi: 10.1002/jcla.24617. Epub 2022 Jul 23.
To investigate the function of PAQR3 in gastric cardia adenocarcinoma (GCA) and understand the possible mechanism of PAQR3 in regulating epithelial-mesenchymal transition (EMT).
We detected PAQR3 protein in 146 GCA tissues and paired normal adjacent tissues (PNTs) specimens using immunohistochemical analysis, and explored its clinical significance. The expression levels of PAQR3 protein in 20 GCA tissues, their paired PNTs, HGC27, SGC7901, and GES-1 cells were analyzed by Western blot. Wild-type PAQR3 was overexpressed in HGC27 cells. The effects of PAQR3 overexpression on the function of HGC27 cells and its underlying mechanisms were then analyzed through a series of cell and molecular biology experiments.
PAQR3 was significantly down-regulated in GCA tissues when compared with paired PNTs (p < 0.0001). The expression level of PAQR3 in GCA tissues was significantly negatively correlated with Helicobacter pylori infection (p = 0.000), venous invasion (p = 0.000), invasion depth (p = 0.000), lymph node metastasis (p = 0.022), tumor stage (p = 0.000), and patient survival (p = 0.009). Downregulation of PAQR3 was highly correlated with increased EMT signature and activated TGF-β/Smad pathway in GCA tissues. Overexpression of PAQR3 in HGC27 cells negatively regulates its cellular functions, such as cell proliferation and migration, and suppresses EMT. Mechanistically, overexpression of PAQR3 significantly down-regulates the protein expression levels of TGF-1, p-Smad2, and p-Smad3 in HGC27 cells.
PAQR3 was significantly down-regulated in GCA tissues, HGC27, and SGC7901 cells. PAQR3 significantly inhibits the proliferation, migration, and invasion of HGC27 cells. Mechanistically, PAQR3 can inhibit the EMT process in HGC27 cells by regulating TGF-β/Smad signaling pathway.
研究 PAQR3 在胃贲门腺癌（GCA）中的作用，探讨 PAQR3 调控上皮间质转化（EMT）的可能机制。
采用免疫组化分析检测 146 例 GCA 组织及配对正常胃黏膜组织（PNTs）中 PAQR3 蛋白的表达，分析其临床意义。采用 Western blot 检测 20 例 GCA 组织及其配对 PNTs、HGC27、SGC7901 和 GES-1 细胞中 PAQR3 蛋白的表达水平。在 HGC27 细胞中转染野生型 PAQR3，观察过表达 PAQR3 对 HGC27 细胞功能的影响，并通过一系列细胞和分子生物学实验探讨其作用机制。
与配对 PNTs 相比，GCA 组织中 PAQR3 表达明显下调（p<0.0001）。GCA 组织中 PAQR3 的表达水平与 H. pylori 感染（p=0.000）、静脉侵袭（p=0.000）、浸润深度（p=0.000）、淋巴结转移（p=0.022）、肿瘤分期（p=0.000）和患者生存（p=0.009）显著负相关。GCA 组织中 PAQR3 的下调与 EMT 标志的增加和 TGF-β/Smad 通路的激活高度相关。在 HGC27 细胞中过表达 PAQR3 可负调控其细胞功能，如细胞增殖和迁移，并抑制 EMT。机制上，PAQR3 过表达可显著下调 HGC27 细胞中 TGF-β1、p-Smad2 和 p-Smad3 的蛋白表达水平。
PAQR3 在 GCA 组织、HGC27 和 SGC7901 细胞中表达下调。PAQR3 显著抑制 HGC27 细胞的增殖、迁移和侵袭。机制上，PAQR3 可能通过调节 TGF-β/Smad 信号通路抑制 HGC27 细胞 EMT 过程。
