Department of Medical Sciences, Graduate School, Soonchunhyang University, Asan, Republic of Korea.
Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan, Republic of Korea.
Anticancer Res. 2024 Oct;44(10):4283-4299. doi: 10.21873/anticanres.17258.
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.
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.
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.
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.
背景/目的：肺腺癌（LUAD）或肺鳞状细胞癌（LUSC）占非小细胞肺癌（NSCLC）的大多数，这些细胞中程序性死亡配体 1（PD-L1）的过表达已知会诱导肿瘤免疫逃逸或耐药性。然而，需要详细研究以确定是否可以降低 PD-L1 表达的 microRNAs（miRNAs）抑制 NSCLC 的耐药性。
Kaplan Meier plotter 和 Receiver Operating Characteristic plotter 用于确定特定 miRNAs 对 NSCLC 患者生存和化疗反应的影响。还进行了细胞活力、集落形成和侵袭测定以及 qPCR 分析。
与正常组相比，LUAD 患者的 miRNA-140-3p（miR-140-3p）表达水平较低，并且 miR-140-3p 表达水平低与 LUAD 患者的不良生存相关，但与 LUSC 无关。miR-140-3p 模拟物抑制 LUAD 细胞的增殖、集落形成和侵袭。有趣的是，在对多西紫杉醇无反应的 LUAD 患者组中，miR-140-3p 的表达明显降低。在 LUAD 细胞中，与单独治疗相比，miR-140-3p 和多西紫杉醇联合治疗显著降低了细胞活力以及与耐药性相关的 ABCG2 和 MVP 基因的表达。此外，与单独使用多西紫杉醇相比，miR-140-3p 模拟物和多西紫杉醇的联合注射显著抑制了肿瘤生长。
这些结果表明，LUAD 中 miR-140-3p 的高表达与患者预后良好相关，并且可能有助于 LUAD 的治疗，特别是通过增加对多西紫杉醇的反应性。
