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盖帕瓦林通过抑制miRNA-3912-3p的表达上调血管生成素样蛋白4(ANGPTL4)的表达来抑制骨肉瘤转移。

Geiparvarin Inhibits OS Metastasis through Upregulation of ANGPTL4 Expression by Inhibiting miRNA-3912-3p Expression.

作者信息

Jiang Fuling, Wang Guang-Jie, Huang Ping, Chen Shu, Xiao He, Zhang Liang, Zou Hua

机构信息

Department of Spine Surgery, Center of Orthopedics, Daping Hospital, Army Medical University, Chongqing 400042, China.

Department of Oncology, The General Hospital of Western Theater Command, Chengdu, Sichuan 610083, China.

出版信息

Evid Based Complement Alternat Med. 2022 Apr 12;2022:4663684. doi: 10.1155/2022/4663684. eCollection 2022.

DOI:10.1155/2022/4663684
PMID:35463073
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9019413/
Abstract

BACKGROUND

Geiparvarin (GN) is a natural compound with anticancer activity. However, the effect of GN on osteosarcoma (OS) and the anticancer mechanism of GN are still unclear.

METHODS

Cell viability was measured by MTT assay. Invasion and migration were measured by transwell assay. The miRNAs, genes, and signaling pathways affected by GN were confirmed by whole-genome sequencing and bioinformatics analysis. The expression level of mRNA and protein was measured by qRT-PCR and western blot. Animal experiment was performed for confirming the GN anticancer effect and side effect .

RESULTS

Our results show that GN significantly inhibits OS cell growth and metastasis . experiment also showed that GN dramatically suppressed OS lung metastasis and no side effects were found. GN treatment inhibited OS metastasis through upregulating the ANGPTL4 expression. In addition, GN inhibited the expression of miR-3912-3p, which targets ANGPTL4.

CONCLUSION

Our data clearly indicate that GN is a candidate drug for OS treatment, and GN plays its role through miR-3912-3p/ANGPTL4 in OS.

摘要

背景

格帕凡林(GN)是一种具有抗癌活性的天然化合物。然而,GN对骨肉瘤(OS)的作用及其抗癌机制仍不清楚。

方法

采用MTT法检测细胞活力。采用Transwell法检测侵袭和迁移能力。通过全基因组测序和生物信息学分析确定受GN影响的微小RNA、基因和信号通路。采用qRT-PCR和蛋白质印迹法检测mRNA和蛋白质的表达水平。进行动物实验以证实GN的抗癌作用和副作用。

结果

我们的结果表明,GN显著抑制OS细胞生长和转移。实验还表明,GN显著抑制OS肺转移,且未发现副作用。GN治疗通过上调ANGPTL4表达抑制OS转移。此外,GN抑制靶向ANGPTL4的miR-3912-3p的表达。

结论

我们的数据清楚地表明,GN是一种用于OS治疗的候选药物,并且GN在OS中通过miR-3912-3p/ANGPTL4发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ed7/9019413/9c837270031c/ECAM2022-4663684.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ed7/9019413/6e6f4b9c0e3e/ECAM2022-4663684.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ed7/9019413/60c42bfbaa37/ECAM2022-4663684.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ed7/9019413/62eefdd72f81/ECAM2022-4663684.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ed7/9019413/3ac38a7af45f/ECAM2022-4663684.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ed7/9019413/9c837270031c/ECAM2022-4663684.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ed7/9019413/6e6f4b9c0e3e/ECAM2022-4663684.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ed7/9019413/60c42bfbaa37/ECAM2022-4663684.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ed7/9019413/62eefdd72f81/ECAM2022-4663684.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ed7/9019413/3ac38a7af45f/ECAM2022-4663684.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ed7/9019413/9c837270031c/ECAM2022-4663684.005.jpg

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ANGPTL4 overexpression inhibits tumor cell adhesion and migration and predicts favorable prognosis of triple-negative breast cancer.ANGPTL4 过表达抑制肿瘤细胞黏附和迁移,并预测三阴性乳腺癌的预后良好。
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