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miR-29a-3p 通过靶向 VEGFA/CD C42/PAK1 抑制子宫内膜癌细胞增殖、迁移和侵袭。

miR-29a-3p inhibits endometrial cancer cell proliferation, migration and invasion by targeting VEGFA/CD C42/PAK1.

机构信息

Department of Gynecology, The Second People's Hospital of Liaocheng, Liaocheng, 252601, Shandong, China.

Department of obstetrics and gynecology, People's Hospital of Rizhao Lanshan, Rizhao, 276807, Shandong, China.

出版信息

BMC Cancer. 2021 Jul 21;21(1):843. doi: 10.1186/s12885-021-08506-z.

DOI:10.1186/s12885-021-08506-z
PMID:34289832
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8293590/
Abstract

BACKGROUND

This study aimed to investigate the mechanism of miR-29a-3p in regulating endometrial cancer (EC) progression.

METHODS

A total of 72 EC patients were enrolled. EC cells were transfected. Cells proliferation, cloning ability, migration and invasion were researched by MTT assay, colony formation experiment, cell scratch test and Transwell experiment respectively. Dual-luciferase reporter assay was performed. Xenograft experiment was conducted using nude mice. miR-29a-3p, VEGFA, CDC42, PAK1 and p-PAK1 expression in cells/tissues was investigated by qRT-PCR and Western blot.

RESULTS

miR-29a-3p expression was aberrantly reduced in EC patients, which was associated with poor outcome. miR-29a-3p inhibited EC cells proliferation, cloning formation, migration and invasion (P <  0.05 or P <  0.01 or P <  0.001). miR-29a-3p inhibited CDC42/PAK1 signaling pathway activity in EC cells (P <  0.01). VEGFA expression was directly inhibited by miR-29a-3p. miR-29a-3p suppressed EC cells malignant phenotype in vitro and growth in vivo by targeting VEGFA/CDC42/PAK1 signaling pathway (P < 0.05 or P < 0.01).

CONCLUSION

miR-29a-3p inhibits EC cells proliferation, migration and invasion by targeting VEGFA/CDC42/PAK1 signaling pathway.

摘要

背景

本研究旨在探讨 miR-29a-3p 调控子宫内膜癌(EC)进展的机制。

方法

纳入 72 例 EC 患者。转染 EC 细胞。通过 MTT 测定法、集落形成实验、细胞划痕实验和 Transwell 实验分别研究细胞增殖、克隆形成能力、迁移和侵袭。进行双荧光素酶报告实验。使用裸鼠进行异种移植实验。通过 qRT-PCR 和 Western blot 检测细胞/组织中 miR-29a-3p、VEGFA、CDC42、PAK1 和 p-PAK1 的表达。

结果

miR-29a-3p 在 EC 患者中表达异常降低,与不良预后相关。miR-29a-3p 抑制 EC 细胞增殖、克隆形成、迁移和侵袭(P<0.05 或 P<0.01 或 P<0.001)。miR-29a-3p 抑制 EC 细胞中 CDC42/PAK1 信号通路活性(P<0.01)。VEGFA 的表达受 miR-29a-3p 直接抑制。miR-29a-3p 通过靶向 VEGFA/CDC42/PAK1 信号通路抑制 EC 细胞的体外恶性表型和体内生长(P<0.05 或 P<0.01)。

结论

miR-29a-3p 通过靶向 VEGFA/CDC42/PAK1 信号通路抑制 EC 细胞的增殖、迁移和侵袭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a14/8293590/c29eb3711672/12885_2021_8506_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a14/8293590/1717a325452d/12885_2021_8506_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a14/8293590/61ccaee8a4cd/12885_2021_8506_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a14/8293590/75820badcc51/12885_2021_8506_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a14/8293590/482097f548a4/12885_2021_8506_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a14/8293590/04533515b453/12885_2021_8506_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a14/8293590/c29eb3711672/12885_2021_8506_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a14/8293590/1717a325452d/12885_2021_8506_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a14/8293590/51cbe040b666/12885_2021_8506_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a14/8293590/dfb7cf0ae0e0/12885_2021_8506_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a14/8293590/61ccaee8a4cd/12885_2021_8506_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a14/8293590/75820badcc51/12885_2021_8506_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a14/8293590/482097f548a4/12885_2021_8506_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a14/8293590/04533515b453/12885_2021_8506_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a14/8293590/c29eb3711672/12885_2021_8506_Fig8_HTML.jpg

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