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环状TSN通过miR-1825/SLC38A2信号轴促进胃癌的增殖和转移。

CircTSN promotes the proliferation and metastasis of gastric cancer through the miR-1825/SLC38A2 signaling axis.

作者信息

Dong Xuqiang, Cheng Tianyu, Zhang Lijun, Song Liqun, Shi Chao

机构信息

Department of Gastrointestinal Surgery, Yixing People's Hospital, Wuxi, Jiangsu, China.

Department of Operating Room, Yixing People's Hospital, Wuxi, Jiangsu, China.

出版信息

Discov Oncol. 2024 Oct 8;15(1):533. doi: 10.1007/s12672-024-01407-0.

Abstract

BACKGROUND

Comprehensive treatment of gastric cancer (GC) is progressing, but the rapid proliferation and metastasis of GC remains a cause of high recurrence and mortality rates. In this study we investigated GC-associated circRNA tending to yield more insight into the mechanisms of gastric cancer development.

METHODS

We detected the expression levels of circTSN in GC tissues and cell lines using qRT-PCR. The circular structure of circTSN was confirmed by Sanger sequencing, agarose gel electrophoresis and RNase R. A series of cell functional experiments were employed to investigate the implication of circTSN aberrant expression on the proliferation and metastasis of GC cells. The predicted binding domain between circTSN and miR-1825 was analyzed by luciferase reporter gene analysis. Meanwhile, subcutaneous tumor xenografts in nude mice were used to validate the role of circTSN in vivo.

RESULTS

It was found that RNA levels of circTSN were significantly elevated in GC tissues and cell lines, which was also confirmed to contain a closed-loop structure. CCK8, clone formation, EdU, transwell and in vivo experiments indicated that the highly expressed circTSN was involved in the proliferation and metastasis process of GC. In addition, circTSN modulates the expression of SLC38A2 by sequence-specific binding to miR-1825.

CONCLUSION

This study identified that circTSN, which is highly expressed in GC, was able to contribute to the proliferation and metastasis of GC cell through miR-1825/SLC38A2 axis and this might provide a new candidate target for the precision treatment of GC.

摘要

背景

胃癌(GC)的综合治疗正在取得进展,但胃癌的快速增殖和转移仍然是导致高复发率和死亡率的原因。在本研究中,我们对与胃癌相关的环状RNA进行了研究,以期更深入地了解胃癌发生的机制。

方法

我们使用qRT-PCR检测了环状TSN(circTSN)在胃癌组织和细胞系中的表达水平。通过桑格测序、琼脂糖凝胶电泳和核糖核酸酶R证实了circTSN的环状结构。采用一系列细胞功能实验来研究circTSN异常表达对胃癌细胞增殖和转移的影响。通过荧光素酶报告基因分析来分析circTSN与miR-1825之间的预测结合域。同时,利用裸鼠皮下肿瘤异种移植模型在体内验证circTSN的作用。

结果

发现circTSN的RNA水平在胃癌组织和细胞系中显著升高,并且也证实其含有闭环结构。CCK8、克隆形成、EdU、transwell实验以及体内实验表明,高表达的circTSN参与了胃癌的增殖和转移过程。此外,circTSN通过与miR-1825的序列特异性结合来调节溶质载体家族38成员2(SLC38A2)的表达。

结论

本研究发现,在胃癌中高表达的circTSN能够通过miR-1825/SLC38A2轴促进胃癌细胞的增殖和转移,这可能为胃癌的精准治疗提供一个新的候选靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f24a/11461732/35c05271b116/12672_2024_1407_Fig1_HTML.jpg

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