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叉头框转录因子 D2 反义 RNA1 通过海绵吸附 miR-204-3p 在食管鳞癌细胞癌中发挥癌基因作用。

FOXD2-AS1 acts an oncogene in esophageal squamous cell carcinoma through sponging miR-204-3p.

机构信息

Department of Thoracic Surgery, Affiliated Tumor Hospital of Xinjiang Medical University, Suzhou Street 789, Ürümqi, 830011, China.

出版信息

Clin Transl Oncol. 2022 Oct;24(10):1954-1963. doi: 10.1007/s12094-022-02850-7. Epub 2022 Jul 1.

DOI:10.1007/s12094-022-02850-7
PMID:35778646
Abstract

PURPOSE

A growing number of evidences has revealed that long non-coding RNAs (lncRNAs) have vital effect in the pathogenesis of esophageal squamous cell carcinoma (ESCC). In our work, we found that lncRNA FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) was significantly increased in clinical ESCC samples and cell lines.

METHODS

The biological effect of FOXD2-AS1 on EC109 and KYSE150 cells showed that the low expression of FOXD2-AS1 inhibited the proliferation through CCK8 and colony formation assays, invasion by transwell chamber test, migration abilities by wound healing assay, and enhance apoptosis rates by flow cytometry assay.

RESULTS

Through bioinformatics analysis and luciferase reporter assays, microRNA (miR)-204-3p was proved to be a target of FOXD2-AS1. We further confirmed that FOXD2-AS1 was the upstream inhibitor of miR-204-3p and the down-regulation of miR-204-3p reversed the repressive effects of low expression of FOXD2-AS1 on ESCC progression. In addition, inhibition of FOXD2-AS1 effectively suppressed the tumor growth.

CONCLUSIONS

In general, our results suggested that FOXD2-AS1 may be of vital therapeutic importance for the treatment of ESCC patients.

摘要

目的

越来越多的证据表明,长链非编码 RNA(lncRNA)在食管鳞状细胞癌(ESCC)的发病机制中具有重要作用。在我们的工作中,我们发现 lncRNA FOXD2 相邻反义链 RNA 1(FOXD2-AS1)在临床 ESCC 样本和细胞系中显著增加。

方法

FOXD2-AS1 对 EC109 和 KYSE150 细胞的生物学效应表明,低表达 FOXD2-AS1 通过 CCK8 和集落形成实验抑制增殖,通过 Transwell 室试验抑制侵袭,通过划痕愈合试验抑制迁移能力,并通过流式细胞术检测提高凋亡率。

结果

通过生物信息学分析和荧光素酶报告基因实验,证明 microRNA(miR)-204-3p 是 FOXD2-AS1 的靶标。我们进一步证实,FOXD2-AS1 是 miR-204-3p 的上游抑制剂,下调 miR-204-3p 逆转了低表达 FOXD2-AS1 对 ESCC 进展的抑制作用。此外,抑制 FOXD2-AS1 有效抑制了肿瘤生长。

结论

总之,我们的结果表明,FOXD2-AS1 可能对 ESCC 患者的治疗具有重要的治疗意义。

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本文引用的文献

1
Silence of FOXD2-AS1 inhibited the proliferation and invasion of esophagus cells by regulating miR-145-5p/CDK6 axis.叉头框转录因子 D2 反义 RNA1 的沉默通过调控 miR-145-5p/细胞周期蛋白依赖性激酶 6 轴抑制食管细胞的增殖和侵袭。
Histol Histopathol. 2020 Sep;35(9):1013-1021. doi: 10.14670/HH-18-232. Epub 2020 Jun 11.
2
LncRNA NR2F1-AS1 promotes proliferation and metastasis of ESCC cells via regulating EMT.长链非编码 RNA NR2F1-AS1 通过调节 EMT 促进 ESCC 细胞的增殖和转移。
Eur Rev Med Pharmacol Sci. 2020 Apr;24(7):3686-3693. doi: 10.26355/eurrev_202004_20831.
3
LncRNA FOXD2-AS1 accelerates the progression of cervical cancer via downregulating CDX1.
长链非编码 RNA FOXD2-AS1 通过下调 CDX1 促进宫颈癌的进展。
Eur Rev Med Pharmacol Sci. 2019 Dec;23(23):10234-10240. doi: 10.26355/eurrev_201912_19660.
4
[FOXD2-AS1 is corelated with clinicopathological parameter of laryngeal carcinoma and promote cancer cell proliferation].[FOXD2-AS1与喉癌临床病理参数相关并促进癌细胞增殖]
Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2019 May;33(5):436-440. doi: 10.13201/j.issn.1001-1781.2019.05.013.
5
Long non‑coding RNA FOXD2‑AS1/miR‑150‑5p/PFN2 axis regulates breast cancer malignancy and tumorigenesis.长非编码 RNA FOXD2-AS1/miR-150-5p/PFN2 轴调控乳腺癌恶性肿瘤发生和肿瘤发生。
Int J Oncol. 2019 Mar;54(3):1043-1052. doi: 10.3892/ijo.2019.4671. Epub 2019 Jan 3.
6
LncRNA SNHG16 predicts poor prognosis in ESCC and promotes cell proliferation and invasion by regulating Wnt/β-catenin signaling pathway.长链非编码 RNA SNHG16 预测 ESCC 预后不良,并通过调节 Wnt/β-连环蛋白信号通路促进细胞增殖和侵袭。
Eur Rev Med Pharmacol Sci. 2018 Jun;22(12):3795-3803. doi: 10.26355/eurrev_201806_15262.
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Long non-coding RNA FOXD2-AS1 functions as a tumor promoter in colorectal cancer by regulating EMT and Notch signaling pathway.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。
Eur Rev Med Pharmacol Sci. 2017 Aug;21(16):3586-3591.