MiR-22-3p Inhibits 5-Fluorouracil Resistance in Cholangiocarcinoma Cells Through PTEN/PI3K/AKT Axis.

IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Assay and drug development technologies Pub Date : 2024-07-01 Epub Date: 2024-07-05 DOI:10.1089/adt.2024.007
Ningrong Zhang, Li Zang
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Abstract

Cholangiocarcinoma (CCA) is a prevalent and highly lethal form of cancer globally. Although microRNAs (miRNAs) have been implicated in the advancement of CCA, their potential influence on 5-fluorouracil (5-Fu) resistance in CCA remains to be fully elucidated. Here, in this study, we investigated the impact of miR-22-3p on CCA resistance. Our investigation involved bioinformatics analysis, which revealed an association between miR-22-3p and the progression, diagnosis, and patient survival of CCA. Furthermore, we validated a notable downregulation of miR-22-3p expression in CCA cell lines. Elevated levels of miR-22-3p inhibit the activity and proliferation of 5-Fu-resistant CCA cell lines. In addition, we confirmed that phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a target gene of miR-22-3p, and its expression correlates with the survival of CCA patients. Reduced PTEN expression enhances apoptosis in 5-Fu-resistant CCA cells. Meanwhile, we verified the existence of the miR-22-3p/PTEN/phosphatidylinositol-3 kinase (PI3K)/Protein kinase B (AKT) regulatory networks in CCA, influencing the sensitivity of CCA cells to 5-Fu. In conclusion, our findings suggest that miR-22-3p acts as a tumor suppressor. Its overexpression inhibits the PTEN/PI3K/AKT axis, promoting cell apoptosis and enhancing CCA sensitivity to 5-Fu.

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MiR-22-3p 通过 PTEN/PI3K/AKT 轴抑制胆管癌细胞的 5-氟尿嘧啶抗性
胆管癌(CCA)是一种全球流行且致死率极高的癌症。尽管微小RNA(miRNA)与CCA的发展有关联,但它们对CCA的5-氟尿嘧啶(5-Fu)耐药性的潜在影响仍有待全面阐明。在本研究中,我们探讨了 miR-22-3p 对 CCA 耐药性的影响。通过生物信息学分析,我们发现 miR-22-3p 与 CCA 的进展、诊断和患者生存之间存在关联。此外,我们还验证了 miR-22-3p 在 CCA 细胞系中的表达明显下调。miR-22-3p水平的升高抑制了对5-Fu耐药的CCA细胞株的活性和增殖。此外,我们还证实了 10 号染色体上缺失的磷酸酶和天丝同源物(PTEN)是 miR-22-3p 的靶基因,其表达与 CCA 患者的存活率相关。PTEN 表达的降低会增强对 5-Fu 抗性的 CCA 细胞的凋亡。同时,我们验证了 miR-22-3p/PTEN/ 磷脂酰肌醇-3 激酶(PI3K)/蛋白激酶 B(AKT)调控网络在 CCA 中的存在,从而影响了 CCA 细胞对 5-Fu 的敏感性。总之,我们的研究结果表明,miR-22-3p 是一种肿瘤抑制因子。它的过表达可抑制 PTEN/PI3K/AKT 轴,促进细胞凋亡,提高 CCA 对 5-Fu 的敏感性。
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来源期刊
Assay and drug development technologies
Assay and drug development technologies 医学-生化研究方法
CiteScore
3.60
自引率
0.00%
发文量
33
审稿时长
>12 weeks
期刊介绍: ASSAY and Drug Development Technologies provides access to novel techniques and robust tools that enable critical advances in early-stage screening. This research published in the Journal leads to important therapeutics and platforms for drug discovery and development. This reputable peer-reviewed journal features original papers application-oriented technology reviews, topical issues on novel and burgeoning areas of research, and reports in methodology and technology application. ASSAY and Drug Development Technologies coverage includes: -Assay design, target development, and high-throughput technologies- Hit to Lead optimization and medicinal chemistry through preclinical candidate selection- Lab automation, sample management, bioinformatics, data mining, virtual screening, and data analysis- Approaches to assays configured for gene families, inherited, and infectious diseases- Assays and strategies for adapting model organisms to drug discovery- The use of stem cells as models of disease- Translation of phenotypic outputs to target identification- Exploration and mechanistic studies of the technical basis for assay and screening artifacts
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