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肿瘤细胞中的线粒体蛋白异亮氨酰 - tRNA合成酶2作为宫颈癌的潜在治疗靶点。

Mitochondrial protein isoleucyl-tRNA synthetase 2 in tumor cells as a potential therapeutic target for cervical cancer.

作者信息

Meng Xiaojiao, Gao Bo, Li Ning

机构信息

Department of Ultrasonic, Zibo Central Hospital, Shandong, China.

出版信息

Cytojournal. 2024 Jun 29;21:22. doi: 10.25259/Cytojournal_17_2024. eCollection 2024.

DOI:10.25259/Cytojournal_17_2024
PMID:38989294
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11234349/
Abstract

OBJECTIVE

Isoleucyl-tRNA synthetase 2 (IARS2) is crucial for mitochondrial activity and function in cancer cells. Cervical cancer is a highly prevalent malignancy affecting the female reproductive system on a global scale. This research investigates the expression and potential roles of IARS2 in cervical cancer cells.

MATERIAL AND METHODS

Initially, we examined the IARS2 expression profile in cervical cancer cells using Western blot technique and quantitative reverse transcription polymerase chain reaction methodologies. Subsequently, cervical cancer cell models with IARS2 silencing and overexpression were constructed using Short Hairpin RNA (ShRNA) (IARS2) and pcMV-FLAG-IARS2, respectively. The impact of IARS2 silencing or overexpression on Hela cell mitochondrial membrane potential, mitochondrial complex I, adenosine triphosphate (ATP) levels, reactive oxygen species activity, viability, proliferation, migration, apoptosis-related proteins, and apoptosis levels was examined through fluorescence staining, enzyme-linked immunosorbent assay, cell counting kit-8 assay, Transwell experiments, Western blot technique, and Terminal deoxynucleotidyl transferase dUTP nick end labeling assay techniques.

RESULTS

The expression of IARS2 is upregulated in cervical cancer cells. Silencing IARS2 with ShRNA (IARS2) disrupts mitochondrial function in cervical cancer cells, resulting in mitochondrial depolarization, heightened oxidative stress, suppression of mitochondrial complex I, and a decrease in ATP levels. Moreover, the depletion of IARS2 significantly impedes the viability, proliferation, and migration of cervical cancer cells, inducing apoptotic processes. In contrast, the overexpression of IARS2 augments the proliferation, migration, and ATP levels in cervical cancer cells.

CONCLUSION

IARS2 plays a pivotal role as a mitochondrial protein in fostering the growth of cervical cancer cells, presenting itself as an innovative target for tumor diagnosis and treatment.

摘要

目的

异亮氨酰 - tRNA合成酶2(IARS2)对癌细胞的线粒体活性和功能至关重要。宫颈癌是一种在全球范围内影响女性生殖系统的高度普遍的恶性肿瘤。本研究调查IARS2在宫颈癌细胞中的表达及潜在作用。

材料与方法

首先,我们使用蛋白质免疫印迹技术和定量逆转录聚合酶链反应方法检测宫颈癌细胞中IARS2的表达谱。随后,分别使用短发夹RNA(ShRNA)(IARS2)和pcMV - FLAG - IARS2构建IARS2沉默和过表达的宫颈癌细胞模型。通过荧光染色、酶联免疫吸附测定、细胞计数试剂盒 - 8测定、Transwell实验、蛋白质免疫印迹技术和末端脱氧核苷酸转移酶dUTP缺口末端标记测定技术,检测IARS2沉默或过表达对Hela细胞线粒体膜电位、线粒体复合体I、三磷酸腺苷(ATP)水平、活性氧物种活性、活力、增殖、迁移、凋亡相关蛋白和凋亡水平的影响。

结果

IARS2在宫颈癌细胞中的表达上调。用ShRNA(IARS2)沉默IARS2会破坏宫颈癌细胞中的线粒体功能,导致线粒体去极化、氧化应激增强、线粒体复合体I受抑制以及ATP水平降低。此外,IARS2的缺失显著阻碍宫颈癌细胞的活力、增殖和迁移,诱导凋亡过程。相反,IARS2的过表达增强了宫颈癌细胞的增殖、迁移和ATP水平。

结论

IARS2作为一种线粒体蛋白在促进宫颈癌细胞生长中起关键作用,是肿瘤诊断和治疗的一个新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09b0/11234349/bb1f7a9b8b48/Cytojournal-21-22-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09b0/11234349/bd351c8b4e6f/Cytojournal-21-22-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09b0/11234349/1bf686ba782e/Cytojournal-21-22-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09b0/11234349/b533c84e0c13/Cytojournal-21-22-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09b0/11234349/92815a8e67a4/Cytojournal-21-22-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09b0/11234349/c6f7528e288d/Cytojournal-21-22-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09b0/11234349/bb1f7a9b8b48/Cytojournal-21-22-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09b0/11234349/bd351c8b4e6f/Cytojournal-21-22-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09b0/11234349/1bf686ba782e/Cytojournal-21-22-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09b0/11234349/b533c84e0c13/Cytojournal-21-22-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09b0/11234349/92815a8e67a4/Cytojournal-21-22-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09b0/11234349/c6f7528e288d/Cytojournal-21-22-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09b0/11234349/bb1f7a9b8b48/Cytojournal-21-22-g006.jpg

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