miR‐29b‐3p targetedly regulates VEGF to inhibit tumor progression and cisplatin resistance through Nrf2/HO‐1 signaling pathway in non‐small cell lung cancer

AbstractBackgroundsNon‐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.