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人源环状RNA YARS与微小RNA-29a-3p相互作用，上调铁调节蛋白2并促进喉鳞状细胞癌进展。

Hsa_circYARS interacts with miR-29a-3p to up-regulate IREB2 and promote laryngeal squamous cell carcinoma progression.

作者信息

Guo Zizhao, Zhao Yuxia, Guo Naicai, Xu Meng, Wang Xiaolei

机构信息

Department of Head and Neck Surgery, National Cancer Center, National Clinical Research Center for Cancer; Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing City, 100021, China.

Department of Radiology, National Cancer Center, National Clinical Research Center for Cancer; Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing City, 100021, China.

出版信息

Discov Oncol. 2024 Sep 3;15(1):401. doi: 10.1007/s12672-024-01198-4.

DOI:10.1007/s12672-024-01198-4
PMID:39225900
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11371998/
Abstract

OBJECTIVE

This study was to investigate the carcinogenic capacity of circYARS in laryngeal squamous cell carcinoma (LSCC) and to reveal its potential mechanism as a competitive endogenous RNA.

METHODS

The differentially expressed circRNA and mRNA in LSCC were detected by RT-qPCR. Dual luciferase reporter assay and RIP were conducted to test the interaction between circYARS, miR-29a-3p, and IREB2. The functional effects of these molecules were investigated by CCK-8, flow cytometry, colony formation assay, Transwell, Western blot, and xenotransplantation mouse models.

RESULTS

In LSCC tissues and cell lines, circYARS and IREB2 levels were enhanced, while miR-29a-3p level was lowered. Depleting circYARS led to decreased IREB2 by promoting miR-29a-3p expression. As a result of miR-29a-3p enhancement or circYARS silence, the proliferative, migratory, and invasion of cancer cells were suppressed and apoptosis was stimulated.

CONCLUSION

circYARS is involved in the tumorigenicity and progression of LSCC through the miR-29a-3p/IREB2 axis, providing strategies and targets for therapeutic intervention of LSCC.

摘要

目的

本研究旨在探讨环状酪氨酸-tRNA合成酶（circYARS）在喉鳞状细胞癌（LSCC）中的致癌能力，并揭示其作为竞争性内源性RNA的潜在机制。

方法

采用逆转录定量聚合酶链反应（RT-qPCR）检测LSCC中差异表达的环状RNA（circRNA）和信使核糖核酸（mRNA）。进行双荧光素酶报告基因检测和RNA免疫沉淀（RIP）实验，以检测circYARS、微小RNA-29a-3p（miR-29a-3p）和铁调节元件结合蛋白2（IREB2）之间的相互作用。通过细胞计数试剂盒-8（CCK-8）、流式细胞术、集落形成实验、Transwell实验、蛋白质免疫印迹法（Western blot）和异种移植小鼠模型研究这些分子的功能作用。

结果

在LSCC组织和细胞系中，circYARS和IREB2水平升高，而miR-29a-3p水平降低。敲低circYARS通过促进miR-29a-3p表达导致IREB2减少。由于miR-29a-3p增强或circYARS沉默，癌细胞的增殖、迁移和侵袭受到抑制，细胞凋亡受到刺激。

结论

circYARS通过miR-29a-3p/IREB2轴参与LSCC的致瘤性和进展，为LSCC的治疗干预提供策略和靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfdd/11371998/3c2da2e28d33/12672_2024_1198_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfdd/11371998/d73034379638/12672_2024_1198_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfdd/11371998/bef3ce9aa5cf/12672_2024_1198_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfdd/11371998/7de19afb4ccc/12672_2024_1198_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfdd/11371998/f10029b42d52/12672_2024_1198_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfdd/11371998/9c123ecc661a/12672_2024_1198_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfdd/11371998/0739a9af4792/12672_2024_1198_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfdd/11371998/3c2da2e28d33/12672_2024_1198_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfdd/11371998/d73034379638/12672_2024_1198_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfdd/11371998/bef3ce9aa5cf/12672_2024_1198_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfdd/11371998/7de19afb4ccc/12672_2024_1198_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfdd/11371998/f10029b42d52/12672_2024_1198_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfdd/11371998/9c123ecc661a/12672_2024_1198_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfdd/11371998/0739a9af4792/12672_2024_1198_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfdd/11371998/3c2da2e28d33/12672_2024_1198_Fig7_HTML.jpg

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