Cell Polarity Protein Pals1-Associated Tight Junction Expression Is a Favorable Prognostic Marker in Clear Cell Renal Cell Carcinoma
Cell Polarity Protein Pals1-Associated Tight Junction Expression Is a Favorable Prognostic Marker in Clear Cell Renal Cell Carcinoma
复制标题
细胞极性蛋白 Pals1 相关的紧密连接表达是透明细胞肾细胞癌的有利预后标志物
DOI：
10.3389/fgene.2020.00931
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发表时间：
2020-08-28
影响因子：
3.7
通讯作者：
Liu, Peijun
中科院分区：
文献类型：
--
作者：
Li, Pingping;Lan, Ping;Liu, Peijun
简介：Pals1 相关紧密连接 (PATJ) 是一种 Crumbs (CRB) 复合体成分，可调节上皮细胞顶端-基底极性和定向迁移。本研究评估了透明细胞肾细胞癌 (ccRCC) 与正常组织中的 PATJ 表达以及与 ccRCC 进展和预后的相关性。方法：体外研究 PATJ 敲低对正常肾上皮细胞活力和蛋白表达的调节作用。 ccRCC 中的 PATJmRNA 数据来自癌症基因组图谱 (TCGA) 和基因表达综合 (GEO) 数据库，并使用 UALCAN、LinkedOmics、Kaplan-Meier Plotter、GEPIA 和 SurvExpress 工具进行分析。对组织微阵列切片中的 PATJ 进行免疫组织化学检查（n = 150 个 ccRCC 和 30 个正常肾脏样本）。用 PATJ 和阴性对照 siRNA 转染正常人肾小管上皮细胞 (HKC) 细胞，进行细胞活力 CCK-8 测定、流式细胞术和蛋白质印迹。结果：数据显示PATJmRNA和蛋白在ccRCC组织和细胞系中表达下调。 PATJ mRNA 的下调与男性患者、晚期肿瘤分期、分级和 ccB 亚型以及患者较差的总体生存率和无病生存率相关。此外，PATJ 蛋白在 ccRCC 组织中也显着下调，并与晚期肿瘤病理学、TNM 分期和整体较差相关。 在体外，PATJ 表达的敲低促进 HKC 增殖和丝裂原激活蛋白激酶 (MAPK) 通路蛋白的激活。结论：本研究表明，ccRCC 中 PATJ 的减少与男性患者、晚期肿瘤和较差的生存率相关，表明 PATJ 可能是 ccRCC 的有用的预后生物标志物和治疗靶点。
Introduction: The Pals1-associated tight junction (PATJ) is a Crumbs (CRB) complex component that regulates epithelial cell apico-basal polarity and directional migration. This study assessed PATJ expression in clear cell renal cell carcinoma (ccRCC) vs. normal tissues and associated with ccRCC progression and prognosis. Methods: The effects of PATJ knockdown were investigated on regulation of normal kidney epithelial cell viability and protein expressionin vitro. ThePATJmRNA data in ccRCC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and analyzed with UALCAN, LinkedOmics, Kaplan-Meier Plotter, GEPIA, and SurvExpress tools. Immunohistochemistry was performed for PATJ in tissue microarray sections (n= 150 ccRCC and 30 normal renal specimens). Normal human kidney tubular epithelial cell (HKC) cells were transfected withPATJand negative control siRNA for cell viability CCK-8 assay, flow cytometry, and western blots. Results: The data showed thatPATJmRNA and protein were downregulated in ccRCC tissues and cell lines. Downregulation ofPATJmRNA was associated with male patients, advanced tumor stages, grades, and ccB subtypes as well as poorer overall and disease-free survival of patients. Furthermore, PATJ protein was also significantly downregulated in ccRCC tissues and associated with advanced tumor pathologic, TNM stages and poorer overall.In vitro, knockdown of PATJ expression promoted HKC proliferation and the activation of mitogen-activated protein kinases (MAPK) pathway proteins. Conclusions: This study revealed that a decrease of PATJ in ccRCC, which was associated with male patients, advanced tumor, and poorer survival, suggesting that PATJ may be a useful prognostic biomarker and therapeutic target for ccRCC.