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circ_ZFR 通过海绵吸附 miR-944 和上调 IL-10 参与紫杉醇耐药调控在宫颈癌中的作用机制研究

circ_ZFR Is Linked to Paclitaxel Resistance in Cervical Cancer via miR-944 Sponging and IL-10 Upregulation.

机构信息

Department of Obstetrics and Gynecology, The First People's Hospital of Wenling, Wenling, 317599 Zhejiang, China.

出版信息

Anal Cell Pathol (Amst). 2022 Jan 27;2022:4807287. doi: 10.1155/2022/4807287. eCollection 2022.

Abstract

OBJECTIVE

Cervical cancer (CC) has an elevated rate of invasion and death despite surgical treatment, radiotherapy, and chemotherapy. Several studies revealed that circRNAs have a key contribution to the resistance of drugs against different types of carcinomas. The goal of the existing study was to figure out what role circ_ZFR plays in paclitaxel (PTX) resistance in cervical cancer (CC) patients.

MATERIALS AND METHODS

Herein, two types of CC cells (SiHa/PTX and Hela/PTX) were utilized. The levels of IL-10 mRNA, miR-944, and circ_ZFR were measured using qRT-PCR analyses. The CCK-8 assay was used to determine PTX resistance. The IL-10 expression was measured via the ELISA technique. The combination of miR-944 and circ_ZFR or IL-10 was validated using a dual-luciferase reporter (DLR) assay.

RESULTS

The amount of circ_ZFR was increased in PTX-resistant CC cells and tissues. In PTX-resistant CC cells, knocking down circ_ZFR expression decreased PTX resistance. circ_ZFR knockdown significantly reduced IL-10 expression via sponging miR-944, increasing PTX sensitivity in PTX-resistant CC cells.

CONCLUSION

circ_ZFR knockdown has a considerable role in overwhelming CC-associated PTX resistance by modifying the axis of miR-944/IL-10 axis, suggesting that developing a circRNA target-based treatment could be considered prevent CC progression.

摘要

目的

尽管进行了手术治疗、放疗和化疗,宫颈癌(CC)的侵袭和死亡率仍然很高。几项研究表明,circRNAs 对不同类型癌的药物耐药性有重要贡献。本研究的目的是研究 circ_ZFR 在宫颈癌(CC)患者紫杉醇(PTX)耐药中的作用。

材料和方法

本研究使用了两种类型的 CC 细胞(SiHa/PTX 和 Hela/PTX)。使用 qRT-PCR 分析测量 IL-10 mRNA、miR-944 和 circ_ZFR 的水平。CCK-8 测定法用于测定 PTX 耐药性。通过 ELISA 技术测量 IL-10 表达。使用双荧光素酶报告(DLR)测定验证 miR-944 和 circ_ZFR 或 IL-10 的组合。

结果

PTX 耐药的 CC 细胞和组织中 circ_ZFR 的量增加。在 PTX 耐药的 CC 细胞中,敲低 circ_ZFR 表达降低了 PTX 耐药性。circ_ZFR 敲低通过海绵吸附 miR-944 显著降低了 IL-10 表达,增加了 PTX 耐药的 CC 细胞的 PTX 敏感性。

结论

circ_ZFR 敲低通过调节 miR-944/IL-10 轴在克服 CC 相关 PTX 耐药中起着重要作用,表明开发基于 circRNA 靶标的治疗方法可能被认为是预防 CC 进展的一种方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f78d/8813297/fafccef256c6/ACP2022-4807287.001.jpg

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