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跨膜和泛素样结构域蛋白 1(TMUB1)通过调节信号转导和转录激活子 1(STAT1)负向调控肝细胞癌增殖。

Transmembrane and Ubiquitin-Like Domain Containing 1 Protein (TMUB1) Negatively Regulates Hepatocellular Carcinoma Proliferation via Regulating Signal Transducer and Activator of Transcription 1 (STAT1).

机构信息

Department of Hepatobiliary Surgery, Daping Hospital, Army Medical University, Chongqing, China (mainland).

Department of Gynaecology and Obstetrics, The 958th Hospital, Southwest Hospital, Army Medical University, Chongqing, China (mainland).

出版信息

Med Sci Monit. 2019 Dec 12;25:9471-9482. doi: 10.12659/MSM.920319.

DOI:10.12659/MSM.920319
PMID:31827061
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6927239/
Abstract

BACKGROUND Hepatocellular carcinoma (HCC) is a common malignancy, but the pathogenesis of HCC is unclear. TMUB1 has an inhibitory effect on normal hepatocytes, but its role in HCC has not been reported. MATERIAL AND METHODS We used immunohistochemistry to observe the expression of transmembrane and ubiquitin-like domain containing 1 protein (TMUB1) and signal transducer and activator of transcription 1 (STAT1) in 132 HCC tissue specimens. The expression of TMUB1, STAT1, and CCND1 in HCC cells were detected by quantitative polymerase chain reaction (qPCR) and western blotting. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used for detecting HCC cells proliferation, and Transwell assays were used for observing the invasion and migration of HCC cells. RESULTS TMUB1 was negatively correlated with HCC pathological malignancy; low expression of TMUB1 indicated poor prognosis. TMUB1 inhibited proliferation but not metastasis in HCC cells. TMUB1 expression was positively correlated with STAT1 in 132 HCC tissues, TMUB1 promoted the expression of STAT1, and suppressed the expression of CCND1 in HCC cells. CONCLUSIONS TMUB1 negatively regulates hepatocellular carcinoma proliferation via regulating STAT1.

摘要

背景

肝细胞癌(HCC)是一种常见的恶性肿瘤,但 HCC 的发病机制尚不清楚。TMUB1 对正常肝细胞具有抑制作用,但尚未报道其在 HCC 中的作用。

材料与方法

我们使用免疫组织化学方法观察了 132 例 HCC 组织标本中跨膜和泛素样结构域蛋白 1(TMUB1)和信号转导子和转录激活子 1(STAT1)的表达。通过定量聚合酶链反应(qPCR)和蛋白质印迹法检测 HCC 细胞中 TMUB1、STAT1 和 CCND1 的表达。使用细胞计数试剂盒-8(CCK-8)和 5-乙炔基-2'-脱氧尿苷(EdU)测定法检测 HCC 细胞的增殖,使用 Transwell 测定法观察 HCC 细胞的侵袭和迁移。

结果

TMUB1 与 HCC 病理恶性程度呈负相关;TMUB1 低表达提示预后不良。TMUB1 在 HCC 细胞中抑制增殖但不抑制转移。TMUB1 的表达与 132 例 HCC 组织中的 STAT1 呈正相关,TMUB1 促进 STAT1 的表达,并抑制 HCC 细胞中 CCND1 的表达。

结论

TMUB1 通过调节 STAT1 负调控肝细胞癌的增殖。

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