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. 2024 Jul;39(7):3956-3966.
doi: 10.1002/tox.24253. Epub 2024 Apr 8.

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

Zhen Sun  1 , Mingming Ren  1 , Jieting Niu  2 , Guojie Tang  1 , Yanguang Li  1 , Fanyi Kong  1 , Xiang Song  1
Affiliations

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

Zhen Sun et al. Environ Toxicol. 2024 Jul.

Abstract

Backgrounds: Non-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.

Methods: We 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.

Results: In 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.

Conclusion: Our 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.

Keywords: VEGF; cisplatin resistance; miR‐29b‐3p; non‐small cell lung cancer.

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REFERENCES

    1. Govindammal M, Prasath M. Vibrational spectra, Hirshfeld surface analysis, molecular docking studies of (RS)‐N,N‐bis(2‐chloroethyl)‐1,3,2‐oxazaphosphinan‐2‐amine 2‐oxide by DFT approach. Heliyon. 2020;6(8):e04641.
    1. Wadowska K, Bil‐Lula I, Trembecki Ł, Śliwińska‐Mossoń M. Genetic markers in lung cancer diagnosis: a review. Int J Mol Sci. 2020;21(13):4569.
    1. Ryu H, Choi HK, Kim HJ, et al. Antitumor activity of a novel tyrosine kinase inhibitor AIU2001 due to abrogation of the DNA damage repair in non‐small cell lung cancer cells. Int J Mol Sci. 2019;20(19):4728.
    1. Jeong D, Ban S, Oh S, Jin Lee S, Yong Park S, Koh YW. Prognostic significance of EDIL3 expression and correlation with mesenchymal phenotype and microvessel density in lung adenocarcinoma. Sci Rep. 2017;7(1):8649.
    1. Wang H, Chen X, Yang B, Xia Z, Chen Q. MiR‐924 as a tumor suppressor inhibits non‐small cell lung cancer by inhibiting RHBDD1/Wnt/β‐catenin signaling pathway. Cancer Cell Int. 2020;20:491.

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