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微小RNA-30b-5p通过表皮生长因子受体/磷脂酰肌醇-3-激酶/蛋白激酶B信号通路靶向多肽N-乙酰半乳糖胺基转移酶7,抑制甲状腺乳头状癌的增殖、侵袭和迁移。

miR-30b-5p inhibits proliferation, invasion, and migration of papillary thyroid cancer by targeting GALNT7 via the EGFR/PI3K/AKT pathway.

作者信息

Wang Ye, Wang Congjun, Fu Zhao, Zhang Siwen, Chen Junqiang

机构信息

The First Affiliated Hospital of Guangxi Medical University, Department of Gastrointestinal Gland Surgery, Nanning, 530021, Guangxi, China.

Guangxi Medical University, Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning, 530021, Guangxi, China.

出版信息

Cancer Cell Int. 2021 Nov 24;21(1):618. doi: 10.1186/s12935-021-02323-x.

DOI:10.1186/s12935-021-02323-x
PMID:34819077
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8611849/
Abstract

BACKGROUND

Papillary thyroid carcinoma (PTC) is a common endocrine tumor. Increasing evidence has shown that microRNA dysfunction is involved in the occurrence and development of cancer. The expression of MicroRNA-30b-5p (miR-30b-5p) was down-regulated in PTC; however, its role in the development of PTC is not clear. Hence, this study aimed to explore the role and mechanism of miR-30b-5p in the occurrence and development of PTC.

METHODS

The qRT-PCR assay was used to detect the expression of miR-30b-5p in 60 cases of papillary thyroid carcinoma along with their matched non-cancerous tissues. This study explored the biological function of miR-30b-5p by the functional gain and loss experiments in vitro and vivo. The direct target gene of miR-30b-5p and its signaling pathway was identified through bioinformatics analysis, qRT-PCR, western blot, rescue experiments, and double luciferase 3'-UTR report analysis.

RESULTS

This study demonstrated that the low expression of miR-30b-5p is related to poor clinicopathological features. Functionally, the overexpression of miR-30b-5p inhibited the proliferation, invasion, and migration of PTC cells. Bioinformatics and luciferase analysis showed that GALNT7 is the direct and functional target of miR-30b-5p. Moreover, miR-30b-5p inhibited the proliferation of PTC in vivo by inhibiting the expression of GALNT7. The studies on the mechanism have shown that GALNT7 promotes cell proliferation and invasion by activating EGFR/PI3K/AKT kinase pathway, which can be attenuated by the kinase inhibitors.

CONCLUSIONS

Overall, miR-30b-5p inhibited the progression of papillary thyroid carcinoma by targeting GALNT7 and inhibiting the EGFR/PI3K/AKT pathway.

摘要

背景

甲状腺乳头状癌(PTC)是一种常见的内分泌肿瘤。越来越多的证据表明,微小RNA功能障碍参与癌症的发生和发展。微小RNA-30b-5p(miR-30b-5p)在PTC中表达下调;然而,其在PTC发生发展中的作用尚不清楚。因此,本研究旨在探讨miR-30b-5p在PTC发生发展中的作用及机制。

方法

采用qRT-PCR法检测60例甲状腺乳头状癌及其配对的癌旁组织中miR-30b-5p的表达。本研究通过体内外功能获得和缺失实验探讨miR-30b-5p的生物学功能。通过生物信息学分析、qRT-PCR、蛋白质免疫印迹法、拯救实验和双荧光素酶3'-UTR报告基因分析鉴定miR-30b-5p的直接靶基因及其信号通路。

结果

本研究表明,miR-30b-5p低表达与不良临床病理特征相关。在功能上,miR-30b-5p过表达抑制PTC细胞的增殖、侵袭和迁移。生物信息学和荧光素酶分析表明,GALNT7是miR-30b-5p的直接功能靶标。此外,miR-30b-5p通过抑制GALNT7的表达在体内抑制PTC的增殖。机制研究表明,GALNT7通过激活EGFR/PI3K/AKT激酶途径促进细胞增殖和侵袭,而激酶抑制剂可减弱该作用。

结论

总体而言,miR-30b-5p通过靶向GALNT7并抑制EGFR/PI3K/AKT途径抑制甲状腺乳头状癌的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d6f/8611849/ec3039079e76/12935_2021_2323_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d6f/8611849/dc84f7018e79/12935_2021_2323_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d6f/8611849/c96d11d20b7f/12935_2021_2323_Fig6_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d6f/8611849/ec3039079e76/12935_2021_2323_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d6f/8611849/3149ec9761e3/12935_2021_2323_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d6f/8611849/5921dbed2ff7/12935_2021_2323_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d6f/8611849/975569d31ca0/12935_2021_2323_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d6f/8611849/78d8e5277a29/12935_2021_2323_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d6f/8611849/dc84f7018e79/12935_2021_2323_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d6f/8611849/c96d11d20b7f/12935_2021_2323_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d6f/8611849/cc9b69a1d5d1/12935_2021_2323_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d6f/8611849/ec3039079e76/12935_2021_2323_Fig8_HTML.jpg

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