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微小RNA-140-3p通过调节FAM83B的稳定性参与胃癌的发生和转移。

miR-140-3p is involved in the occurrence and metastasis of gastric cancer by regulating the stability of FAM83B.

作者信息

Wang Zhengguang, Chen Ke, Li Dongchang, Chen Mengding, Li Angqing, Wang Jian

机构信息

Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Shushan District, Hefei, 230022, Anhui, China.

Anhui Medical University, Shushan District, Hefei, 230001, Anhui, China.

出版信息

Cancer Cell Int. 2021 Oct 16;21(1):537. doi: 10.1186/s12935-021-02245-8.

Abstract

BACKGROUND

Gastric cancer (GC) is a malignant tumor and microRNAs (miRNAs) are closely connected to GC development. The purpose of this study is to investigate the effect of miR-140-3p on the occurrence and metastasis of GC.

METHODS

We detected miR-140-3p expression in GC cells and tissues. The correlation between miR-140-3p and prognosis and clinicopathological features in GC was analyzed. The role of miR-140-3p in GC cell migration, invasion, and proliferation was analyzed. The model of tumor transplantation and metastasis in nude mice was established, and the effect of miR-140-3p on the development and metastasis of GC was assessed. The relation between miR-140-3p and SNHG12 and the relations among HuR, SNHG12, and FAM83B were analyzed.

RESULTS

miR-140-3p was poorly expressed in GC. GC patients with low miR-140-3p expression had a poor prognosis and unfavorable clinicopathologic features. Overexpression of miR-140-3p inhibited GC cell migration, invasion, and proliferation, and inhibited the development and metastasis of GC. miR-140-3p directly bound to SNHG12 in GC tissues and downregulated SNHG12 expression. SNHG12 overexpression induced HuR nuclear transportation. HuR can bind to FAM83B and up-regulate the mRNA level of FAM83B. Overexpression of SNHG12 or FAM83B reduced the inhibition of overexpression of miR-140-3p on GC.

CONCLUSION

miR-140-3p directly bound to SNHG12 in GC and down-regulated the expression of SNHG12, reduced the binding of SNHG12 and HuR, thus inhibiting the nuclear transportation of HuR and the binding of HuR and FAM83B, and reducing the transcription of FAM83B, and finally inhibiting the growth and metastasis of GC.

摘要

背景

胃癌(GC)是一种恶性肿瘤,微小RNA(miRNA)与胃癌的发生发展密切相关。本研究旨在探讨miR-140-3p对胃癌发生和转移的影响。

方法

我们检测了胃癌细胞和组织中miR-140-3p的表达。分析了miR-140-3p与胃癌预后及临床病理特征之间的相关性。分析了miR-140-3p在胃癌细胞迁移、侵袭和增殖中的作用。建立了裸鼠肿瘤移植和转移模型,评估了miR-140-3p对胃癌发生和转移的影响。分析了miR-140-3p与SNHG12的关系以及HuR、SNHG12和FAM83B之间的关系。

结果

miR-140-3p在胃癌中低表达。miR-140-3p表达低的胃癌患者预后较差,临床病理特征不佳。miR-140-3p的过表达抑制了胃癌细胞的迁移、侵袭和增殖,并抑制了胃癌的发生和转移。miR-140-3p在胃癌组织中直接与SNHG12结合并下调SNHG12的表达。SNHG12的过表达诱导HuR核转运。HuR可与FAM83B结合并上调FAM83B的mRNA水平。SNHG12或FAM83B的过表达降低了miR-140-3p过表达对胃癌的抑制作用。

结论

miR-140-3p在胃癌中直接与SNHG12结合并下调SNHG12的表达,减少SNHG12与HuR的结合,从而抑制HuR的核转运以及HuR与FAM83B的结合,降低FAM83B的转录,最终抑制胃癌的生长和转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce3e/8520196/48395fe411a8/12935_2021_2245_Fig1_HTML.jpg

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