BackgroundsNon‐small cell lung carcinoma (NSCLC) is a common type of lung cancer. Prior investigations have elucidated the pivotal role of miR‐29b‐3p in restraining tumor growth and metastasis. Nonetheless, it remains to be determined whether miR‐29b‐3p can effectively suppress NSCLC progression and enhance the sensitivity of NSCLC cells to cisplatin. This investigation sought to determine the mechanism by which miR‐29b‐3p inhibited the advancement of NSCLC and mitigated resistance to cisplatin.MethodsWe initially assessed miR‐29b‐3p and VEGF levels in NSCLC tissues and cell lines. Next, miR‐29b‐3p expression was elevated in NSCLC cell lines H1975 and A549 by overexpression plasmid transfection. Following this, a sequence of molecular biology experiments was conducted to evaluate the impact of miR‐29b‐3p on the biological behaviors of NSCLC cells and their resistance to cisplatin. Additionally, we predicted VEGF was a target gene of miR‐29b‐3p by bioinformatics analysis. We next employed western blot to evaluate the protein expression of Nrf2 and HO‐1 in NSCLC cells. Finally, we elucidated the effects of VEGF and Nrf2/HO‐1pathway on NSCLC progression and cisplatin resistance by in vitro assays.ResultsIn comparison to paracancerous tissues and human normal lung epithelial cells, the expression of miR‐29b‐3p was notably reduced and VEGF expression was clearly elevated in NSCLC tissues and cells. Moreover, miR‐29b‐3p upregulated obviously suppressed the biological activities of NSCLC cells and increased their sensitivity to cisplatin. Furthermore, in NSCLC cells, miR‐29b‐3p bound to VEGF and negatively regulate its transcription. Additionally, miR‐29b‐3p overexpression also inhibited the Nrf2/HO‐1 signaling pathway. Finally, the overexpression of VEGF and the activation of the Nrf2/HO‐1 pathway reversed miR‐29b‐3p‐mediated inhibitory effect on biological behaviors of NSCLC cells and increased the cisplatin resistance.ConclusionOur findings indicate that miR‐29b‐3p impedes NSCLC cells' biological behaviors and augments their sensitivity to cisplatin by targeting VEGF to modulate the Nfr2/HO‐1 signaling pathway.

中文翻译：

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miR-29b-3p通过Nrf2/HO-1信号通路靶向调节VEGF抑制非小细胞肺癌肿瘤进展和顺铂耐药

背景非小细胞肺癌（NSCLC）是一种常见的肺癌类型。先前的研究已经阐明了 miR-29b-3p 在抑制肿瘤生长和转移中的关键作用。尽管如此，miR-29b-3p是否能够有效抑制NSCLC进展并增强NSCLC细胞对顺铂的敏感性仍有待确定。本研究旨在确定 miR-29b-3p 抑制 NSCLC 进展并减轻对顺铂耐药的机制。方法我们最初评估了 NSCLC 组织和细胞系中的 miR-29b-3p 和 VEGF 水平。接下来，通过过表达质粒转染，NSCLC 细胞系 H1975 和 A549 中 miR-29b-3p 表达升高。随后，进行了一系列分子生物学实验，以评估 miR-29b-3p 对 NSCLC 细胞生物学行为及其对顺铂耐药性的影响。此外，我们通过生物信息学分析预测VEGF是miR-29b-3p的靶基因。接下来我们采用蛋白质印迹法来评估 NSCLC 细胞中 Nrf2 和 HO-1 的蛋白表达。最后，我们通过体外实验阐明了VEGF和Nrf2/HO-1通路对NSCLC进展和顺铂耐药的影响。结果与癌旁组织和人正常肺上皮细胞相比，miR-29b-3p的表达显着降低，VEGF的表达显着降低。 NSCLC组织和细胞中的表达明显升高。此外，miR-29b-3p上调明显抑制NSCLC细胞的生物学活性并增加其对顺铂的敏感性。此外，在 NSCLC 细胞中，miR-29b-3p 与 VEGF 结合并负向调节其转录。此外，miR-29b-3p过表达也抑制Nrf2/HO-1信号通路。最后，VEGF 的过表达和 Nrf2/HO-1 通路的激活逆转了 miR-29b-3p 介导的对 NSCLC 细胞生物学行为的抑制作用，并增加了顺铂耐药性。结论我们的研究结果表明 miR-29b-3p 阻碍 NSCLC通过靶向 VEGF 调节 Nfr2/HO-1 信号通路来调节细胞的生物学行为并增强其对顺铂的敏感性。