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微小RNA-3121-3p通过抑制甲状腺乳头状癌中的Rap1GAP促进肿瘤侵袭和转移。

MiR-3121-3p promotes tumor invasion and metastasis by suppressing Rap1GAP in papillary thyroid cancer .

作者信息

Xu Ming, Zhou Jun, Zhang Qiulei, Le Kehao, Xi Zihan, Yi Pengfei, Zhao Xiangwang, Tan Jie, Huang Tao

机构信息

Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Ann Transl Med. 2020 Oct;8(19):1229. doi: 10.21037/atm-20-4469.

DOI:10.21037/atm-20-4469
PMID:33178761
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7607113/
Abstract

BACKGROUND

Rap1GAP is a tumor suppressor and is downregulated in human malignancies including papillary thyroid cancer (PTC). The mechanism of its suppression in PTC remains unclear.

METHODS

Bioinformatic analyses were carried out to evaluate clinical significance and to predict upstream miRNA bindings of Rap1GAP. Three PTC cell lines, TPC-1, B-CPAP, and K1, were employed for functional verification and further experiments. We used dual-luciferase reporter gene assay to confirm the miRNA binding prediction, Western blotting and quantitative polymerase chain reaction (qPCR) to explore miRNA and Rap1GAP regulation, Transwell and wound healing assays to compare cell migration and invasion after protein knockout or overexpression, and Cell Counting Kit-8 (CCK-8) assay to evaluate cell proliferation.

RESULTS

Rap1GAP expression was suppressed in thyroid cancer compared to adjacent normal tissues and was a potential diagnostic marker of PTC. Rap1GAP suppression was correlated to younger age, advanced T stage, N stage, extrathyroidal extension, BRAF-like tumors, and higher risk of recurrence. Combined analysis of bioinformatic prediction and dual-luciferase assay revealed binding between miR-3121-3p with 3'UTR of Rap1GAP promoter. MiR-3121-3p promoted cell migration, invasion, and proliferation via inhibiting Rap1GAP and thus upregulating MAPK pathway. Overexpression and knockdown of Rap1GAP could counteract the influence on cell migration and invasion carried out by miR-3121-3p mimic and inhibitor, respectively. Rap1GAP partially impaired the effect of miR-3121-3p in cell growth in the CCK-8 assay.

CONCLUSIONS

Rap1GAP expression is suppressed in PTC and is a potential diagnostic marker. Its upstream regulator, miR-3121-3p, affects tumor metastasis and proliferation via regulating Rap1GAP expression. MAPK signaling pathway may be involved in this effect.

摘要

背景

Rap1GAP是一种肿瘤抑制因子，在包括甲状腺乳头状癌（PTC）在内的人类恶性肿瘤中表达下调。其在PTC中发挥抑制作用的机制尚不清楚。

方法

进行生物信息学分析以评估临床意义并预测Rap1GAP的上游miRNA结合位点。采用三种PTC细胞系TPC-1、B-CPAP和K1进行功能验证及进一步实验。我们使用双荧光素酶报告基因检测来确认miRNA结合预测结果，采用蛋白质印迹法和定量聚合酶链反应（qPCR）来探究miRNA与Rap1GAP的调控关系，通过Transwell实验和伤口愈合实验比较蛋白质敲除或过表达后细胞的迁移和侵袭能力，并使用细胞计数试剂盒-8（CCK-8）实验评估细胞增殖能力。

结果

与相邻正常组织相比，Rap1GAP在甲状腺癌中的表达受到抑制，并且是PTC的一个潜在诊断标志物。Rap1GAP表达受抑制与患者年龄较轻、T分期较晚、N分期较晚、甲状腺外侵犯、BRAF样肿瘤以及更高的复发风险相关。生物信息学预测与双荧光素酶检测的联合分析揭示了miR-3121-3p与Rap1GAP启动子3'UTR之间存在结合。miR-3121-3p通过抑制Rap1GAP从而上调MAPK通路，促进细胞迁移、侵袭和增殖。Rap1GAP的过表达和敲低分别可以抵消miR-3121-3p模拟物和抑制剂对细胞迁移和侵袭的影响。在CCK-8实验中，Rap1GAP部分削弱了miR-3121-3p对细胞生长的影响。

结论

Rap1GAP在PTC中表达受抑制，是一种潜在的诊断标志物。其上游调节因子miR-3121-3p通过调节Rap1GAP的表达影响肿瘤转移和增殖。MAPK信号通路可能参与了这一作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2fe/7607113/2c02f4ef370b/atm-08-19-1229-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2fe/7607113/3347062edbe8/atm-08-19-1229-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2fe/7607113/75f83fcd4c81/atm-08-19-1229-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2fe/7607113/479374e305c5/atm-08-19-1229-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2fe/7607113/b65f598d9b4b/atm-08-19-1229-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2fe/7607113/c14cd1c64d0c/atm-08-19-1229-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2fe/7607113/2c02f4ef370b/atm-08-19-1229-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2fe/7607113/3347062edbe8/atm-08-19-1229-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2fe/7607113/75f83fcd4c81/atm-08-19-1229-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2fe/7607113/479374e305c5/atm-08-19-1229-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2fe/7607113/b65f598d9b4b/atm-08-19-1229-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2fe/7607113/c14cd1c64d0c/atm-08-19-1229-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2fe/7607113/2c02f4ef370b/atm-08-19-1229-f6.jpg

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1
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2
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FEBS J. 2019 Jun;286(12):2277-2294. doi: 10.1111/febs.14802. Epub 2019 Mar 18.
3
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4
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5
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Med Oncol. 2023 Jul 31;40(9):258. doi: 10.1007/s12032-023-02098-3.
6
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7
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4
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5
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6
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7
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8
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9
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10
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