Hsa_circ_0003220通过调节miR-489-3p/IGF1驱动人NSCLC细胞的化疗耐药

Shaofeng Xia, Chenliang Wang
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摘要

在越来越多的研究中,环状rna (circRNAs)已被证明在癌症的发展和治疗耐药性中起着关键作用。目的是探讨hsa_circ_0003220在非小细胞肺癌(NSCLC)化疗耐药中的作用和过程。本研究选用非小细胞肺癌细胞系H460和A549。hsa_circ_0003220, miR-489-3p和胰岛素样生长因子(IGF1) mRNA水平通过定量实时聚合酶链反应(qRT-PCR)进行评估。采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑测定顺铂、多西他赛和紫杉醇(PTX)耐药,酶联免疫吸附试验(ELISA)测定IGF1表达。为了证实miR-489-3p与hsa_circ_0003220或IGF1的关系,我们采用了双荧光素酶报告方法。hsa_circ_0003220水平在ptx耐药(PR) NSCLC的细胞和组织中升高。在PR型NSCLC细胞中,hsa_circ_0003220敲除可降低化疗耐药。机制研究的目的是,hsa_circ_0003220敲低通过miR-489-3p海绵作用显著降低IGF1的表达,降低PR NSCLC细胞的化疗耐药。通过控制miR-489-3p/IGF1轴,hsa_circ_0003220敲低有助于NSCLC克服化疗耐药,提示潜在的circrna靶向治疗该疾病。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Hsa_circ_0003220 Drives Chemoresistance of Human NSCLC Cells by Modulating miR-489-3p/IGF1

Circular RNAs (circRNAs) have been shown to have critical roles in developing cancer and treatment resistance in an increasing body of research. The aim was to look into the functions and processes of hsa_circ_0003220 in the non-small cell lung cancer (NSCLC) chemoresistance. The NSCLC cell lines H460 and A549 were employed in present work. hsa_circ_0003220, miR-489-3p, and insulin-like growth factors (IGF1) mRNA levels were assessed with a quantitative real time polymerase chain reaction (qRT-PCR). The cisplatin, docetaxel, and paclitaxel (PTX) resistances were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and the enzyme linked immunosorbent assay (ELISA) test measured IGF1 expression. In order to corroborate the miR-489-3p relation with hsa_circ_0003220 or IGF1, a dual-luciferase reporter method was applied. The level of hsa_circ_0003220 was raised in cells and tissues from PTX-resistant (PR) NSCLC. In PR NSCLC cells, hsa_circ_0003220 knockdown reduced chemoresistance. For the purpose of the mechanism study, hsa_circ_0003220 knockdown substantially reduced IGF1 expression via miR-489-3p sponging, reducing chemoresistance in PR NSCLC cells. By controlling the miR-489-3p/IGF1 axis, hsa_circ_0003220 knockdown helped NSCLC overcome chemoresistance, suggesting a potential circRNA-targeted therapy for the disease.

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Comparative and Functional Genomics
Comparative and Functional Genomics 生物-生化与分子生物学
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