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长链非编码 RNA H19 通过激活 Wnt/β-连环蛋白信号通路促进胃癌中的上皮间质转化和转移。

LncRNA H19 Promoted the Epithelial to Mesenchymal Transition and Metastasis in Gastric Cancer via Activating Wnt/β-Catenin Signaling.

机构信息

Department of General Surgery, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

出版信息

Dig Dis. 2022;40(4):436-447. doi: 10.1159/000518627. Epub 2021 Jul 27.

Abstract

BACKGROUND

Due to a combination of high morbidity and lack of effective treatments, gastric cancer (GC) remains a major cause of cancer-related death all over the world. H19, as a paternally imprinted long noncoding RNA (lncRNA), has been found dysregulated in GC.

AIM

The aim of this study is to elucidate the specific mechanism of H19 in GC.

METHODS

Bioinformatic analysis and quantitative real-time PCR analysis were utilized to test the expression pattern of H19 in GC tissues and cell lines. Wound healing, transwell, immunofluorescence assay, and Western blot assays were conducted to test cell malignant phenotypes. Meanwhile, TOP/FOP flash assay was to analyze the relationship of H19 and Wnt/β-catenin signaling. Also, mice xenograft models were to evaluate the influence of H19 on tumor growth.

RESULTS

H19 was overexpressed in GC tissues and cell lines and related to poor prognosis for GC patients. In vitro and in vivo assays verified the promotion of H19 on GC cell epithelial to mesenchymal transition (EMT) and metastasis. Mechanistically, H19 could induce β-catenin to transfer into nucleus and activate Wnt/β-catenin signaling, thus promoting EMT and metastasis of GC cells.

CONCLUSION

Our findings proved the mechanism of H19-mediated metastasis via activating Wnt/β-catenin signaling, which provides a promising target for developing new therapeutic strategies in GC.

摘要

背景

由于高发病率和缺乏有效治疗方法的综合影响,胃癌(GC)仍然是全世界癌症相关死亡的主要原因。H19 作为一种印迹的长非编码 RNA(lncRNA),已在 GC 中发现失调。

目的

本研究旨在阐明 H19 在 GC 中的具体作用机制。

方法

利用生物信息学分析和实时定量 PCR 分析检测 GC 组织和细胞系中 H19 的表达模式。进行划痕愈合、transwell、免疫荧光分析和 Western blot 分析检测细胞恶性表型。同时,TOP/FOP flash 分析用于分析 H19 与 Wnt/β-catenin 信号通路的关系。另外,还进行了小鼠异种移植模型实验以评估 H19 对肿瘤生长的影响。

结果

H19 在 GC 组织和细胞系中过度表达,并与 GC 患者的不良预后相关。体外和体内实验验证了 H19 对 GC 细胞上皮间质转化(EMT)和转移的促进作用。机制上,H19 可以诱导β-catenin 转位入核并激活 Wnt/β-catenin 信号通路,从而促进 GC 细胞的 EMT 和转移。

结论

我们的研究结果证明了 H19 通过激活 Wnt/β-catenin 信号通路介导转移的机制,为开发 GC 的新治疗策略提供了有前途的靶点。

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