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揭示hsa_circ_0007439：一种通过miR-556-5p/PTEN轴发挥作用的新型鼻咽癌抑制因子。

Unveiling hsa_circ_0007439: a novel suppressor of nasopharyngeal carcinoma via miR-556-5p/PTEN Axis.

作者信息

Li Ming, Yang Jing, Feng WanRong, Fu DongXue, Bai Yang

机构信息

Department of Surgery, Beidahuang Group General Hospital, Branch 1, Harbin, 150000, Heilongjiang, China.

Departments of Cardiology II, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China.

出版信息

Discov Oncol. 2024 Dec 18;15(1):807. doi: 10.1007/s12672-024-01656-z.

DOI:10.1007/s12672-024-01656-z
PMID:39692840
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11655796/
Abstract

OBJECTIVE

There has been no explanation for the exact mechanism of circRNAs in nasopharyngeal carcinoma (NPC). Circ_0007439 was investigated in this study to determine its role and mechanism in NPC.

METHODS

To identify circ_0007439, microRNA (miR)-556-5p, and PTEN mRNA in NPC tissues and cells, RT-qPCR was employed. PTEN protein was quantified using western blot analysis. The impact of circ_0007439 on cellular activities was assessed using CCK-8, colony formation, Transwell, and flow cytometry, in that order. The interaction of miR-556-5p with circ_0007439 or PTEN mRNA was confirmed through a dual luciferase reporter gene assay and RIP assay.

RESULTS

circ_0007439 and PTEN levels were low in NPC tissues and cells, while miR-556-5p was highly expressed. NPC cells were inhibited in proliferation, migration, invasion, and anti-apoptosis when circ_0007439 was upregulated or miR-556-5p was reduced. The circ_0007439 molecule acted as a molecular sponge that inhibited miR-556-5p's suppression of PTEN expression. Additionally, reduction of PTEN weakened the inhibitive effects of elevating circ_0007439 or reducing miR-556-5p on NPC cells.

CONCLUSION

Circ_0007439 mediates miR-556-5p/PTEN axis to inhibit NPC progression as an potential target for NPC therapy.

摘要

目的

环状RNA（circRNA）在鼻咽癌（NPC）中的具体作用机制尚不清楚。本研究旨在探究circ_0007439在NPC中的作用及其机制。

方法

采用逆转录定量聚合酶链反应（RT-qPCR）检测NPC组织和细胞中circ_0007439、微小RNA（miR）-556-5p和PTEN信使核糖核酸（mRNA）的表达。采用蛋白质免疫印迹法检测PTEN蛋白表达水平。依次采用细胞计数试剂盒-8（CCK-8）法、集落形成实验、Transwell实验和流式细胞术评估circ_0007439对细胞活性的影响。通过双荧光素酶报告基因实验和RNA免疫沉淀实验（RIP）验证miR-556-5p与circ_0007439或PTEN mRNA之间的相互作用。

结果

NPC组织和细胞中circ_0007439和PTEN水平较低，而miR-556-5p高表达。上调circ_0007439或降低miR-556-5p可抑制NPC细胞的增殖、迁移、侵袭及抗凋亡能力。circ_0007439分子作为分子海绵，可抑制miR-556-5p对PTEN表达的抑制作用。此外，PTEN表达降低可减弱上调circ_0007439或降低miR-556-5p对NPC细胞的抑制作用。

结论

circ_0007439通过介导miR-556-5p/PTEN轴抑制NPC进展，有望成为NPC治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d11/11655796/86d4ecfa0275/12672_2024_1656_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d11/11655796/4565166ab417/12672_2024_1656_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d11/11655796/ce563bd25f8e/12672_2024_1656_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d11/11655796/f0ff45681904/12672_2024_1656_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d11/11655796/fb33017314ca/12672_2024_1656_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d11/11655796/de8770f5b8db/12672_2024_1656_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d11/11655796/86d4ecfa0275/12672_2024_1656_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d11/11655796/4565166ab417/12672_2024_1656_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d11/11655796/ce563bd25f8e/12672_2024_1656_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d11/11655796/f0ff45681904/12672_2024_1656_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d11/11655796/fb33017314ca/12672_2024_1656_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d11/11655796/de8770f5b8db/12672_2024_1656_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d11/11655796/86d4ecfa0275/12672_2024_1656_Fig6_HTML.jpg

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本文引用的文献

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Circular RNA COL1A1 promotes Warburg effect and tumor growth in nasopharyngeal carcinoma.环状RNA COL1A1促进鼻咽癌的瓦伯格效应和肿瘤生长。
Discov Oncol. 2024 Apr 15;15(1):120. doi: 10.1007/s12672-024-00941-1.
2
Hsa_circ_0003356 suppresses gastric cancer progression via miR-556-5p/FKBP5 axis.人源环状RNA Hsa_circ_0003356通过miR-556-5p/FKBP5轴抑制胃癌进展。
Toxicol In Vitro. 2024 May;97:105787. doi: 10.1016/j.tiv.2024.105787. Epub 2024 Feb 22.
3
Hsa_circ_0136666 stimulates gastric cancer progression and tumor immune escape by regulating the miR-375/PRKDC Axis and PD-L1 phosphorylation.
Hsa_circ_0136666 通过调控 miR-375/PRKDC 轴和 PD-L1 磷酸化促进胃癌进展和肿瘤免疫逃逸。
Mol Cancer. 2023 Dec 13;22(1):205. doi: 10.1186/s12943-023-01883-y.
4
Circular RNA EFR3A promotes nasopharyngeal carcinoma progression through modulating the miR-654-3p/EFR3A axis.环状 RNA EFR3A 通过调节 miR-654-3p/EFR3A 轴促进鼻咽癌的进展。
Cell Mol Biol (Noisy-le-grand). 2023 Nov 30;69(12):111-117. doi: 10.14715/cmb/2023.69.12.18.
5
Hsa_circ_0009092/miR-665/NLK signaling axis suppresses colorectal cancer progression via recruiting TAMs in the tumor microenvironment.hsa_circ_0009092/miR-665/NLK 信号轴通过在肿瘤微环境中募集 TAMs 来抑制结直肠癌的进展。
J Exp Clin Cancer Res. 2023 Nov 27;42(1):319. doi: 10.1186/s13046-023-02887-8.
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Hsa_circ_0070661 inhibits cancer progression through miR-556-5p/TEK axis in lung adenocarcinoma.Hsa_circ_0070661通过miR-556-5p/TEK轴抑制肺腺癌的癌症进展。
Cancer Biomark. 2023;37(1):53-66. doi: 10.3233/CBM-220282.
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Novel long non-coding RNA lncAMPC downregulates PTEN via miR-214 to promote nasopharyngeal carcinoma progression.新型长链非编码 RNA lncAMPC 通过 miR-214 下调 PTEN 促进鼻咽癌进展。
Mol Cell Biochem. 2022 Mar;477(3):805-814. doi: 10.1007/s11010-021-04323-x. Epub 2022 Jan 21.
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J Gene Med. 2022 Jan;24(1):e3391. doi: 10.1002/jgm.3391. Epub 2021 Nov 11.