miR-4734 Targets BMP7 to Accelerate Non-Small Cell Lung Cancer Progression and Serves as a Poor Prognostic Biomarker

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Abstract

Background NSCLC is a leading cause of cancer mortality worldwide, highlighting the need for non-invasive biomarkers. Circulating miRNAs are promising candidates due to their stability in serum. Methods This study measured serum levels of miR-4734 using qRT-PCR in NSCLC patients and healthy controls. The diagnostic ability was assessed through ROC analysis, while the prognostic significance was evaluated with Kaplan–Meier survival curves and Cox regression. Functional assays, including CCK-8, ELISA, Transwell, and tube formation tests, were conducted to examine the role of miR-4734 in cell proliferation and angiogenesis in NSCLC and endothelial cells. BMP7 was identified as a direct target of miR-4734 via bioinformatic predictions, dual-luciferase reporter assays, and rescue experiments. Results Serum miR-4734 was significantly elevated in patients with NSCLC compared to healthy controls, demonstrating moderate diagnostic accuracy with an AUC of 0.787 (95% CI: 0.721–0.853). High levels of miR-4734 were linked to advanced TNM stage and shorter overall survival. Moreover, miR-4734 served as an independent adverse prognostic factor, with an HR of 2.103 (95% CI: 1.091–4.051). Functionally, miR-4734 encouraged cell proliferation in NSCLC, increased the secretion of pro-angiogenic factors, and boosted endothelial cell migration and tube formation. Mechanistically, miR-4734 directly targeted and inhibited BMP7, and the oncogenic effects of miR-4734 were partly reversed when BMP7 was overexpressed. Conclusion Serum miR-4734 serves as a potential non-invasive biomarker for diagnosing and predicting NSCLC outcomes. It promotes tumor growth by increasing proliferation and angiogenesis through directly inhibiting BMP7.

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