Hsa_circ_0003489 Drives PTX Resistance of Human NSCLC Cells Through Modulating miR-98-5p/IGF2.

IF 1.8 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pharmacogenomics & Personalized Medicine Pub Date : 2023-01-01 DOI:10.2147/PGPM.S416360
Shaofeng Xia, Chenliang Wang
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Abstract

Background: Circular RNAs (circRNAs) demonstrated critical roles within developing tumors and treatment resistance in an increasing body of research. The aim was to look into the functions and processes of hsa_circ_0003489 in the non-small cell lung cancer (NSCLC) paclitaxel (PTX) resistance.

Methods: NSCLC cell-based cultures including A549 and H460 were employed for such an investigation. hsa_circ_0003489, miR-98-5p, and insulin-like growth factor 2 (IGF2) expression-profiles were evaluated with a quantitative real-time polymerase chain reaction (RT-qPCR). The PTX resistance was determined using MTT assay, and the ELISA test measured IGF2 expression. Facilitating corroboration for miR-98-5p relation and hsa_circ_0003489 or IGF2, a dual-luciferase reporter method was applied.

Results: The hsa_circ_0003489 level was raised in cells and tissues from PTX-resistant (PR) NSCLC. In PR NSCLC cells, hsa_circ_0003489 knockdown reduced PTX resistance. For the purpose of the mechanism study, hsa_circ_0003489 knockdown substantially reduced IGF2 expression via miR-98-5p sponging, improving PTX sensitivity in PR NSCLC.

Conclusion: Through miR-98-5p/IGF2 axis control, hsa_circ_0003489 knockdown helped NSCLC overcome PTX resistance, suggesting a potential circRNA-targeted therapy for the disease.

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Hsa_circ_0003489通过调节miR-98-5p/IGF2驱动人NSCLC细胞PTX抗性
背景:在越来越多的研究中,环状rna (circRNAs)在肿瘤的发生和治疗耐药性中发挥了关键作用。目的是探讨hsa_circ_0003489在非小细胞肺癌(NSCLC)紫杉醇(PTX)耐药中的功能和过程。方法:采用A549、H460等非小细胞肺癌细胞培养物进行研究。hsa_circ_0003489, miR-98-5p和胰岛素样生长因子2 (IGF2)的表达谱通过定量实时聚合酶链反应(RT-qPCR)进行评估。MTT法检测PTX耐药,ELISA法检测IGF2表达。为了验证miR-98-5p与hsa_circ_0003489或IGF2之间的关系,我们采用了双荧光素酶报告方法。结果:hsa_circ_0003489水平在ptx耐药(PR) NSCLC细胞和组织中升高。在PR型NSCLC细胞中,敲低hsa_circ_0003489可降低PTX耐药性。机制研究的目的是,hsa_circ_0003489敲低通过miR-98-5p海绵显著降低IGF2表达,提高PTX在PR NSCLC中的敏感性。结论:通过miR-98-5p/IGF2轴控制,hsa_circ_0003489敲低有助于NSCLC克服PTX耐药,提示潜在的circrna靶向治疗该疾病。
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来源期刊
Pharmacogenomics & Personalized Medicine
Pharmacogenomics & Personalized Medicine Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
3.30
自引率
5.30%
发文量
110
审稿时长
16 weeks
期刊介绍: Pharmacogenomics and Personalized Medicine is an international, peer-reviewed, open-access journal characterizing the influence of genotype on pharmacology leading to the development of personalized treatment programs and individualized drug selection for improved safety, efficacy and sustainability. In particular, emphasis will be given to: Genomic and proteomic profiling Genetics and drug metabolism Targeted drug identification and discovery Optimizing drug selection & dosage based on patient''s genetic profile Drug related morbidity & mortality intervention Advanced disease screening and targeted therapeutic intervention Genetic based vaccine development Patient satisfaction and preference Health economic evaluations Practical and organizational issues in the development and implementation of personalized medicine programs.
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