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长链非编码 RNA LINC00675 通过抑制食管鳞癌细胞中的 Wnt/β-catenin 信号通路抑制肿瘤发生和 EMT。

Long non-coding RNA LINC00675 inhibits tumorigenesis and EMT via repressing Wnt/β-catenin signaling in esophageal squamous cell carcinoma.

机构信息

Emergency Department, Shenzhen People's Hospital, the Second Medical College of Jinan University, Shenzhen, Guangdong, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Dec;22(23):8288-8297. doi: 10.26355/eurrev_201812_16526.

Abstract

OBJECTIVE

Long noncoding RNA LINC00675 (LINC00675) seems to play an anti-oncogenic role in cancers, though its exact function remains unknown. Up to date, little is known about the role of LINC00675 in esophageal squamous cell carcinoma (ESCC). In this study, we aimed to explore the expression pattern, clinical significance and biological function of LINC00675 in ESCC.

PATIENTS AND METHODS

RT-PCR was performed to detect the expression levels of LINC00675 in both ESCC tissue and cell lines. The association of LINC00675 expression with clinicopathological factors and prognosis was statistically analyzed. Cell growth was detected by MTT assay and colony formation assay. Cell apoptosis was evaluated with flow cytometry. Migration and invasion ability of ESCC cells were detected wound healing assay and transwell assays. The expressions of EMT-related proteins and Wnt/β-catenin-related proteins by Western blot were investigated.

RESULTS

LINC00675 expression was significantly downregulated in both ESCC tissues and cell lines. Decreased LINC00675 expression was correlated with histological grade, lymph nodes metastasis and advanced clinical stage. Furthermore, LINC00675 could serve as an independent predictor for overall survival in ESCC. Importantly, in vitro experiments indicated that that forced LINC00675 expression significantly suppressed inhibited ESCC cell proliferation, colony formation, migration, invasion and EMT, and promoted cell apoptosis through suppressing Wnt/β-catenin signaling pathway.

CONCLUSIONS

We suggested that LINC00675 acted as a tumor suppressor in ESCC via regulation of Wnt/β-catenin signaling pathway and may be a new prognostic biomarker and potential therapeutic target for ESCC intervention.

摘要

目的

长链非编码 RNA LINC00675(LINC00675)似乎在癌症中发挥抑癌作用,但确切功能尚不清楚。迄今为止,关于 LINC00675 在食管鳞状细胞癌(ESCC)中的作用知之甚少。在这项研究中,我们旨在探讨 LINC00675 在 ESCC 中的表达模式、临床意义和生物学功能。

患者和方法

采用 RT-PCR 检测 ESCC 组织和细胞系中 LINC00675 的表达水平。统计分析 LINC00675 表达与临床病理因素和预后的关系。MTT 法和集落形成实验检测细胞生长。流式细胞术检测细胞凋亡。划痕愈合实验和 Transwell 实验检测 ESCC 细胞的迁移和侵袭能力。Western blot 检测 EMT 相关蛋白和 Wnt/β-catenin 相关蛋白的表达。

结果

LINC00675 在 ESCC 组织和细胞系中的表达均显著下调。LINC00675 表达降低与组织学分级、淋巴结转移和临床晚期有关。此外,LINC00675 可作为 ESCC 总生存的独立预测因子。重要的是,体外实验表明,强制表达 LINC00675 可显著抑制 ESCC 细胞增殖、集落形成、迁移、侵袭和 EMT,并通过抑制 Wnt/β-catenin 信号通路促进细胞凋亡。

结论

我们认为,LINC00675 通过调节 Wnt/β-catenin 信号通路在 ESCC 中发挥肿瘤抑制作用,可能成为 ESCC 干预的新预后生物标志物和潜在治疗靶点。

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