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长链非编码 RNA FOXD2-AS1 通过调节 EMT 和 Notch 信号通路在结直肠癌中发挥肿瘤促进作用。

Long non-coding RNA FOXD2-AS1 functions as a tumor promoter in colorectal cancer by regulating EMT and Notch signaling pathway.

机构信息

Department of Pathophysiology, Basic Medical Science, Shanxi Medical University, Taiyuan, Shanxi, China.

出版信息

Eur Rev Med Pharmacol Sci. 2017 Aug;21(16):3586-3591.

PMID:28925486
Abstract

OBJECTIVE

A growing number of long noncoding RNAs (lncRNAs) are emerging as new modulators in cancer origination and progression. However, the functions and molecular mechanisms of lncRNAs to colorectal cancer (CRC) are still largely unknown. The aim of this study was to investigate the function and role of lncRNA FOXD2-AS1 (FOXD2-AS1) in human CRC.

PATIENTS AND METHODS

The expression of FOXD2-AS1 was investigated using Real-time reverse transcription-polymerase chain reaction (qRT-PCR) in 45 CRC specimens and matched adjacent normal tissues and CRC cell lines. MTT assays were conducted to explore the impact of FOXD2-AS1 knockdown on the proliferation of human CRC cells. The effects of FOXD2-AS1 on CRC cell migration and invasion were evaluated by cell invasion assays and migration assays. Western blot analysis was used to determine the expression levels of EMT-related and Notch-related proteins.

RESULTS

The results showed that FOXD2-AS1 expression was significantly increased in CRC tissues as well as in CRC cell lines. Moreover, down-regulation of FOXD2-AS1 suppressed cell, proliferation, invasion and migration in vitro. Importantly, we further confirmed that EMT and the Notch signaling pathway were inactivated in CRC cells after FOXD2-AS1 knockdown.

CONCLUSIONS

FOXD2-AS1 promoted the progression of CRC by regulating EMT and Notch signaling pathway. Thus, targeting FOXD2-AS1 may be an effective strategy for CRC treatment.

摘要

目的

越来越多的长链非编码 RNA(lncRNA)被发现是癌症发生和发展的新型调节因子。然而,lncRNA 对结直肠癌(CRC)的功能和分子机制仍知之甚少。本研究旨在探讨 lncRNA FOXD2-AS1(FOXD2-AS1)在人 CRC 中的功能和作用。

患者和方法

使用实时逆转录-聚合酶链反应(qRT-PCR)检测 45 例 CRC 标本和匹配的相邻正常组织及 CRC 细胞系中 FOXD2-AS1 的表达。MTT 法检测 FOXD2-AS1 敲低对人 CRC 细胞增殖的影响。细胞侵袭实验和迁移实验评估 FOXD2-AS1 对 CRC 细胞迁移和侵袭的影响。Western blot 分析用于确定 EMT 相关和 Notch 相关蛋白的表达水平。

结果

结果表明,FOXD2-AS1 在 CRC 组织和 CRC 细胞系中表达明显增加。此外,FOXD2-AS1 下调抑制了细胞体外增殖、侵袭和迁移。重要的是,我们进一步证实,FOXD2-AS1 敲低后 CRC 细胞中 EMT 和 Notch 信号通路被激活。

结论

FOXD2-AS1 通过调节 EMT 和 Notch 信号通路促进 CRC 的进展。因此,靶向 FOXD2-AS1 可能是 CRC 治疗的有效策略。

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