LncRNA AFAP1-AS1 exhibits oncogenic characteristics and promotes gemcitabine-resistance of cervical cancer cells through miR-7-5p/EGFR axis.

IF 2 4区医学 Q3 ONCOLOGY

Oncology Research Pub Date : 2024-11-13 eCollection Date: 2024-01-01 DOI:10.32604/or.2024.044547

Chaoqun Wang, Ting Zhang, Chaohe Zhang

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引用次数: 0

Abstract

Background: Drug resistance is the main factor contributing to cancer recurrence and poor prognosis. Exploration of drug resistance-related mechanisms and effective therapeutic targets are the aim of molecular targeted therapy. In our study, the role of long non-coding RNA (lncRNA) AFAP1-AS1 in gemcitabine resistance and related mechanisms were explored in cervical cancer cells.

Methods: Gemcitabine-resistant cervical cancer cell lines HT-3-Gem and SW756-Gem were constructed using the gemcitabine concentration gradient method. The overall survival rates and recurrence-free survival rates were evaluated by Kaplan-Meier analysis. The interaction was verified through a Dual-luciferase reporter gene assay and a Biotinylated RNA pull-down assay. Cell proliferation ability was assessed through methyl-thiazolyl-tetrazolium (MTT), soft agar, and colony formation experiments. Cell cycle and apoptosis were detected by flow cytometry.

Results: Up-regulation of AFAP1-AS1 in cervical cancer predicted a poor prognosis. Besides, patients in the gemcitabine-resistance group had higher levels of AFAP1-AS1 than the gemcitabine-sensitive group. AFAP1-AS1 promoted tumor growth and induced gemcitabine tolerance of cervical cancer cells. In addition, AFAP1-AS1 mediated epidermal growth factor receptor (EGFR) expression by serving as a molecular sponge for microRNA-7a-5p (miR-7-5p). This present study also proved that the knockdown of EGFR or overexpression of miR-7a-5p abolished the accelerative role of AFAP1-AS1 overexpression in cancer progression and gemcitabine tolerance.

Conclusions: In general, the AFAP1-AS1/miR-7-5p/EGFR axis was tightly related to the progression and gemcitabine tolerance of cervical cancer, providing potential targets for the management of cervical cancer.

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LncRNA AFAP1-AS1 具有致癌特性，并通过 miR-7-5p/EGFR 轴促进宫颈癌细胞对吉西他滨的耐药性。

背景：耐药性是导致癌症复发和预后不良的主要因素。探索耐药相关机制和有效治疗靶点是分子靶向治疗的目标。本研究探讨了宫颈癌细胞中长非编码 RNA（lncRNA）AFAP1-AS1 在吉西他滨耐药中的作用及相关机制：方法：采用吉西他滨浓度梯度法构建了吉西他滨耐药的宫颈癌细胞系HT-3-Gem和SW756-Gem。采用 Kaplan-Meier 分析法评估了总生存率和无复发生存率。通过双荧光素酶报告基因试验和生物素化 RNA 拉取试验验证了相互作用。细胞增殖能力通过甲基-噻唑基-四唑啉（MTT）、软琼脂和菌落形成实验进行评估。流式细胞术检测细胞周期和细胞凋亡：结果：AFAP1-AS1在宫颈癌中的上调预示着预后不良。此外，吉西他滨耐药组患者的AFAP1-AS1水平高于吉西他滨敏感组。AFAP1-AS1能促进肿瘤生长，诱导宫颈癌细胞对吉西他滨耐受。此外，AFAP1-AS1通过充当microRNA-7a-5p（miR-7-5p）的分子海绵，介导表皮生长因子受体（EGFR）的表达。本研究还证明，敲除表皮生长因子受体或过表达 miR-7a-5p 可消除 AFAP1-AS1 过表达在癌症进展和吉西他滨耐受中的加速作用：总的来说，AFAP1-AS1/miR-7-5p/EGFR轴与宫颈癌的进展和吉西他滨耐受性密切相关，为宫颈癌的治疗提供了潜在靶点。

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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来源期刊

Oncology Research 医学-肿瘤学

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.