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CD82/KAI1 通过 TGF-β1 抑制食管鳞癌细胞的侵袭和转移。

CD82/KAI1 inhibits invasion and metastasis of esophageal squamous cell carcinoma via TGF-β1.

机构信息

Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Sep;22(18):5928-5937. doi: 10.26355/eurrev_201809_15922.

DOI:10.26355/eurrev_201809_15922
PMID:30280774
Abstract

OBJECTIVE

Previous studies have found that CD82/KAI1 is a tumor suppressor gene. However, the role of CD82/KAI1 in esophageal squamous cell carcinoma (ESCC) has not been reported. This study aims to investigate the specific role of CD82/KAI1 in ESCC, so as to further explore the relationship between CD82/KAI1 expression and clinical characteristics of ESCC.

PATIENTS AND METHODS

The expression of CD82/KAI1 in 96 pairs of ESCC tissues and adjacent normal tissues was detected by Real-time quantitative polymerase chain reaction (qRT-PCR). The relationship between CD82/KAI1 expression and the pathological indicators of ESCC patients was analyzed by Kaplan-Meier method. QRT-PCR further validated the expression level of CD82/KAI1 in ESCC cells. In addition, the CD82/KAI1 knockdown expression model was constructed using small interfering RNA in ESCC cell lines TE-1 and EC-109 cells. Cell counting kit-8 (CCK-8) and transwell assay were performed to detect cell viability, invasion and migration. Finally, the potential mechanism of CD82/KAI1 in regulating ESCC was explored using Western blot.

RESULTS

QRT-PCR results showed that the expression level of CD82/KAI1 in ESCC was significantly lower than that of normal tissues, and the difference was statistically significant. Higher rates of lymph node metastasis and distant metastasis, as well as shorter overall survival were observed in ESCC patients with lower expression of CD82/KAI1 compared with those with higher expression. CD82/KAI1 overexpression decreased cell proliferation, invasion and metastasis in ESCC cells. Western blot results showed that the expressions of TGF-β1, Smad2/3, MMP-2 and MMP-9 were regulated by CD82/KAI1. In addition, rescue experiments demonstrated an interaction between CD82/KAI1 and TGF-β1, indicating that CD82/KAI1 inhibits the malignant progression of ESCC via regulating TGF-β1.

CONCLUSIONS

Lowly expressed CD82/KAI1 in ESCC was significantly associated with the pathological stage, distant metastasis and poor prognosis of ESCC patients. CD82/KAI1 may inhibit the malignant progression of ESCC by interacting with TGF-β1.

摘要

目的

先前的研究发现 CD82/KAI1 是一种肿瘤抑制基因。然而,CD82/KAI1 在食管鳞状细胞癌(ESCC)中的作用尚未得到报道。本研究旨在探讨 CD82/KAI1 在 ESCC 中的具体作用,从而进一步探讨 CD82/KAI1 表达与 ESCC 临床特征之间的关系。

患者和方法

通过实时定量聚合酶链反应(qRT-PCR)检测 96 对 ESCC 组织和相邻正常组织中 CD82/KAI1 的表达。采用 Kaplan-Meier 法分析 CD82/KAI1 表达与 ESCC 患者病理指标的关系。qRT-PCR 进一步验证了 ESCC 细胞中 CD82/KAI1 的表达水平。此外,采用小干扰 RNA 在 ESCC 细胞系 TE-1 和 EC-109 细胞中构建 CD82/KAI1 敲低表达模型。采用细胞计数试剂盒-8(CCK-8)和 Transwell 实验检测细胞活力、侵袭和迁移。最后,采用 Western blot 探讨 CD82/KAI1 调节 ESCC 的潜在机制。

结果

qRT-PCR 结果显示,ESCC 中 CD82/KAI1 的表达水平明显低于正常组织,差异具有统计学意义。与 CD82/KAI1 高表达的 ESCC 患者相比,CD82/KAI1 低表达的 ESCC 患者淋巴结转移和远处转移率更高,总生存期更短。CD82/KAI1 过表达可降低 ESCC 细胞的增殖、侵袭和转移。Western blot 结果显示,TGF-β1、Smad2/3、MMP-2 和 MMP-9 的表达受 CD82/KAI1 调节。此外,挽救实验表明 CD82/KAI1 与 TGF-β1 之间存在相互作用,表明 CD82/KAI1 通过调节 TGF-β1 抑制 ESCC 的恶性进展。

结论

ESCC 中 CD82/KAI1 的低表达与 ESCC 患者的病理分期、远处转移和不良预后显著相关。CD82/KAI1 可能通过与 TGF-β1 相互作用抑制 ESCC 的恶性进展。

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