MiR-140-3p 通过抑制肺腺癌中 PD-L1/ABCG2/MVP 的表达提高多西他赛的敏感性

IF 1.6 4区 医学 Q4 ONCOLOGY Anticancer research Pub Date : 2024-10-01 DOI:10.21873/anticanres.17258
Minji Kwon, Dayeon Lim, Jayeon Park, World Gil, Jiwoo Jung, Suyeon Jung, Chaeeon Kim, Minjeong Go, Ye Hwang Cheong, Hee Sun Park, Yong-Bin Eom, Sin-Aye Park
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引用次数: 0

摘要

背景/目的:肺腺癌(LUAD)或肺鳞癌(LUSC)占非小细胞肺癌(NSCLC)的大多数,已知这些细胞中程序性死亡配体1(PD-L1)的过度表达可诱导肿瘤免疫逃避或耐药性。然而,要确定减少PD-L1表达的微RNA(miRNA)是否能抑制NSCLC的耐药性,还需要进行详细的研究:采用 Kaplan Meier plotter 和 Receiver Operating Characteristic plotter 来确定特定 miRNA 对 NSCLC 患者生存和化疗反应的影响。此外,还进行了细胞活力、集落形成和侵袭测定以及 qPCR 分析:结果:与正常组相比,miRNA-140-3p(miR-140-3p)在LUAD患者中的表达量较低。miR-140-3p模拟物抑制了LUAD细胞的增殖、集落形成和侵袭。有趣的是,在对多西他赛无反应的LUAD患者组中,miR-140-3p的表达明显较低。在 LUAD 细胞中,miR-140-3p 和多西他赛联合治疗与单独使用其中一种治疗方法相比,能显著降低细胞活力以及与耐药性相关的基因 ABCG2 和 MVP 的表达。此外,与单独使用多西他赛相比,联合注射 miR-140-3p mimic 和多西他赛可明显抑制肿瘤生长:这些结果表明,miR-140-3p 在 LUAD 中的高表达与患者的良好预后相关,可能有助于 LUAD 的治疗,尤其是通过增加对多西他赛的反应性。
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MiR-140-3p Improves Sensitivity to Docetaxel by Suppressing PD-L1/ABCG2/MVP Expression in Lung Adenocarcinoma.

Background/aim: Lung adenocarcinoma (LUAD) or lung squamous cell carcinoma (LUSC) accounts for the majority of non-small cell lung cancer (NSCLC), and overexpression of programmed death ligand 1 (PD-L1) in these cells is known to induce tumor immune evasion or drug resistance. However, detailed studies are needed to determine whether microRNAs (miRNAs) that reduce PD-L1 expression can suppress drug resistance in NSCLC.

Materials and methods: Kaplan Meier plotter and Receiver Operating Characteristic plotter were used to determine the effect of specific miRNAs on survival and chemotherapy response in NSCLC patients. Cell viability, colony formation and invasion assays, and qPCR analyses were also performed.

Results: The expression of miRNA-140-3p (miR-140-3p) was lower in LUAD patients, compared to the normal group, and low expression of miR-140-3p was associated with poor survival of LUAD patients, but not in LUSC. The miR-140-3p mimic inhibited proliferation, colony formation, and invasion of LUAD cells. Interestingly, the expression of miR-140-3p was significantly lower in the group of LUAD patients who did not respond to docetaxel. In LUAD cells, combined treatment with miR-140-3p and docetaxel significantly reduced cell viability as well as the expression of ABCG2 and MVP, genes associated with drug resistance, compared to either treatment alone. Additionally, combined injection of miR-140-3p mimic and docetaxel significantly inhibited tumor growth compared to treatment with docetaxel alone.

Conclusion: These results suggest that the high expression of miR-140-3p in LUAD is correlated with good patient prognosis and may contribute to the treatment of LUAD, especially by increasing responsiveness to docetaxel.

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来源期刊
Anticancer research
Anticancer research 医学-肿瘤学
CiteScore
3.70
自引率
10.00%
发文量
566
审稿时长
2 months
期刊介绍: ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed. ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies). Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.
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