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在结直肠癌中,miR-491-5p通过靶向IGF2发挥肿瘤抑制作用。

miR-491-5p functions as a tumor suppressor by targeting IGF2 in colorectal cancer.

作者信息

Lu Lei, Cai Ming, Peng Meixia, Wang Fei, Zhai Xiaofeng

机构信息

Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu, China,

出版信息

Cancer Manag Res. 2019 Feb 22;11:1805-1816. doi: 10.2147/CMAR.S183085. eCollection 2019.

Abstract

BACKGROUND

Dysregulation of miRNAs is critically implicated in tumorigenesis, and aberrant expression of miR-491-5p has been reported to play a key role in initiation and progression of various cancers. However, the biological function and underlying mechanism of miR-491-5p in colorectal cancer (CRC) remain elusive.

METHODS

Quantitative real-time PCR (qRT-PCR) was employed to evaluate the levels of miR-491-5p and IGF2 mRNA expression in CRC tissues, cell lines and plasma. Cell counting kit-8 and colony formation assays were used to detect the effects of miR-491-5p on CRC cell growth. Luciferase reporter assays were applied to confirm the miR-491-5p target gene. In vivo experiments were conducted in nude mice.

RESULTS

miR-491-5p was found to be obviously downregulated in CRC tissues and cell lines, and decreased miR-491-5p expression level was shown to be associated with differentiation, TNM stage and poor overall survival (OS). miR-491-5p overexpression suppressed CRC cell proliferation both in vitro and in vivo. Mechanically, insulin-like growth factor 2 (IGF2) was identified to be a direct target of miR-491-5p in CRC cells, and overexpression of IGF2 rescued the miR-491-5p-induced suppression of proliferation in CRC cells. Finally, we demonstrated that plasma miR-491-5p expression was decreased in CRC when compared to healthy controls and might be an effective diagnostic biomarker for CRC.

CONCLUSION

These data showed that miR-491-5p functioned as a tumor suppressor by targeting IGF2 in CRC, and miR-491-5p could serve as a potential diagnostic and prognostic biomarker for CRC.

摘要

背景

微小RNA(miRNA)的失调在肿瘤发生中至关重要,据报道miR-491-5p的异常表达在各种癌症的发生和发展中起关键作用。然而,miR-491-5p在结直肠癌(CRC)中的生物学功能和潜在机制仍不清楚。

方法

采用定量实时聚合酶链反应(qRT-PCR)评估CRC组织、细胞系和血浆中miR-491-5p和胰岛素样生长因子2(IGF2)mRNA的表达水平。使用细胞计数试剂盒-8和集落形成试验检测miR-491-5p对CRC细胞生长的影响。应用荧光素酶报告基因试验来确认miR-491-5p的靶基因。在裸鼠中进行体内实验。

结果

发现miR-491-5p在CRC组织和细胞系中明显下调,且miR-491-5p表达水平降低与分化、TNM分期及总体生存率差相关。miR-491-5p过表达在体外和体内均抑制CRC细胞增殖。机制上,胰岛素样生长因子2(IGF2)被确定为CRC细胞中miR-491-5p的直接靶标,IGF2过表达挽救了miR-491-5p诱导的CRC细胞增殖抑制。最后,我们证明与健康对照相比,CRC患者血浆中miR-491-5p表达降低,且其可能是CRC的一种有效的诊断生物标志物。

结论

这些数据表明,miR-491-5p在CRC中通过靶向IGF2发挥肿瘤抑制作用,且miR-491-5p可作为CRC潜在的诊断和预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5133/6391127/524c0e26f436/cmar-11-1805Fig1.jpg

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