LncRNA AFAP1-AS1 Induces Gefitinib Resistance of Lung Adenocarcinoma Through the miR-653-5p/AGR2 Axis.

IF 2.3 3区医学 Q2 HEALTH CARE SCIENCES & SERVICES

Therapeutics and Clinical Risk Management Pub Date : 2023-01-05 eCollection Date: 2023-01-01 DOI:10.2147/TCRM.S374162

Tao Zuo, Ping Jiang, Jun Fu, Yongjian Zhang

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Abstract

Purpose: Gefitinib resistance limits the therapeutic efficacy of gefitinib to lung adenocarcinoma (LUAD). The goal of this research is to learn more about the lncRNA AFAP1-AS1 and how it functions in gefitinib-resistant LUAD cells.

Methods: RT-qPCR was performed to test the expression of AFAP1-AS1, miR-653-5p and AGR2 in LUAD tissues with acquired resistance to gefitinib or not as well as in gefitinib-resistant LUAD cells. Cell proliferation, invasion and apoptosis were measured by CCK8 assays, transwell invasion assays and flow cytometry, respectively. Luciferase reporter assay showed that miR-653-5p and AFAP1-AS1 or AGR2 interactions.

Results: In gefitinib-resistant LUAD cells and tissues, AFAP1-AS1 was overexpressed. Meanwhile, silencing AFAP1-AS1 reduced proliferation and migration while increasing apoptosis and gefitinib sensitivity. Mechanically, AFAP1-AS1 sequestered the miR-653-5p and blocked the inhibition of miR-653-5p to AGR2 and stepwise upregulated AGR2 overexpression in LUAD gefitinib resistant cells, resulting gefitinib resistance in LUAD.

Conclusion: AFAP1-AS1 promotes gefitinib-resistance LUAD cells through a previously unrecognized miR-653-5p/AGR2 axis, suggesting targeting AFAP1-AS1/miR-653-5p/AGR2 axis might be a promising way for LUAD intervention.

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LncRNA AFAP1-AS1 通过 miR-653-5p/AGR2 轴诱导吉非替尼对肺腺癌的耐药性

目的：吉非替尼耐药限制了吉非替尼对肺腺癌（LUAD）的疗效。本研究的目的是进一步了解 lncRNA AFAP1-AS1 及其在吉非替尼耐药的 LUAD 细胞中的功能：方法：采用RT-qPCR检测AFAP1-AS1、miR-653-5p和AGR2在吉非替尼获得性耐药或非获得性耐药LUAD组织以及吉非替尼耐药LUAD细胞中的表达。细胞增殖、侵袭和凋亡分别通过 CCK8 检测法、Transwell 侵袭检测法和流式细胞术进行检测。荧光素酶报告实验表明，miR-653-5p与AFAP1-AS1或AGR2相互作用：结果：在吉非替尼耐药的LUAD细胞和组织中，AFAP1-AS1表达过高。同时，沉默 AFAP1-AS1 可减少细胞增殖和迁移，同时增加细胞凋亡和吉非替尼敏感性。从机理上讲，AFAP1-AS1封存了miR-653-5p，阻断了miR-653-5p对AGR2的抑制作用，并逐步上调了AGR2在LUAD吉非替尼耐药细胞中的过表达，导致吉非替尼在LUAD中耐药：结论：AFAP1-AS1通过之前尚未认识到的miR-653-5p/AGR2轴促进吉非替尼耐药的LUAD细胞，这表明靶向AFAP1-AS1/miR-653-5p/AGR2轴可能是干预LUAD的一种有前景的方法。

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来源期刊

Therapeutics and Clinical Risk Management HEALTH CARE SCIENCES & SERVICES-

CiteScore

4.80

自引率

3.60%

发文量

139

审稿时长

16 weeks

期刊介绍： Therapeutics and Clinical Risk Management is an international, peer-reviewed journal of clinical therapeutics and risk management, focusing on concise rapid reporting of clinical studies in all therapeutic areas, outcomes, safety, and programs for the effective, safe, and sustained use of medicines, therapeutic and surgical interventions in all clinical areas. The journal welcomes submissions covering original research, clinical and epidemiological studies, reviews, guidelines, expert opinion and commentary. The journal will consider case reports but only if they make a valuable and original contribution to the literature. As of 18th March 2019, Therapeutics and Clinical Risk Management will no longer consider meta-analyses for publication. The journal does not accept study protocols, animal-based or cell line-based studies.