[Clinical Study of MiR-125b-5p/HIF-1α Pathway in Involvement of Vitamin D Deficiency in Pathogenesis of Multiple...

To detect the serum levels of 25(OH)D, miR-125b-5p, hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor A (VEGFA) in patients with multiple myeloma (MM), and explore the role of miR-125b-5p/HIF-1α pathway in the involvement of vitamin D deficiency in the pathogenesis of MM.

Fifty three newly diagnosed/relapsed MM patients admitted to the department of hematology of our hospital from October 2021 to December 2023 were included. Meanwhile, 25 healthy individuals matched in gender and age from our hospital's Health Management Center were selected as controls. The serum level of 25(OH)D was monitored by mass spectrometry, the serum level of miR-125b-5p was detected by real-time fluorescence quantitative PCR, and serum levels of HIF-1α and VEGFA were measured by enzyme-linked immunosorbent assay. The levels of 25(OH)D, miR-125b-5p, HIF-1α, and VEGFA were compared between the two groups. According to the level of 25(OH)D, the MM patients were divided into vitamin D deficiency group (< 20 ng/ml) and vitamin D non-deficiency group (≥20 ng/ml), and the levels of miR-125b-5p, HIF-1α, and VEGFA were compared between the two groups. The correlations between 25(OH)D, miR-125b-5p, HIF-1α and VEGFA were analyzed. The receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of 25(OH)D combined with miR-125b-5p for newly diagnosed MM.

The level of 25(OH)D in MM patients was significantly lower than that in control group (P < 0.01). There was no significant difference in 25(OH)D level between newly diagnosed and relapsed MM patients (P >0.05). Compared with the control group, the level of miR-125b-5p was significantly reduced in MM patients (P < 0.01), while the levels of HIF-1α and VEGFA were significantly increased (both P < 0.001). In MM patients, the miR-125b-5p level in the vitamin D deficiency group was significantly decreased than that in the non-deficiency group (P < 0.01), while the levels of HIF-1α and VEGFA were significantly increased (both P < 0.05). In MM patients, 25(OH)D was positively correlated with miR-125b-5p, while negatively correlated with HIF-1α and VEGFA (both P < 0.05). Moreover, miR-125b-5p was negatively correlated with HIF-1α and VEGFA (both P < 0.05). The area under the curve (AUC) for diagnosing MM with 25(OH)D, miR-125b-5p, and their combination were 0.699, 0.751, and 0.791, respectively.

The incidence of vitamin D deficiency is high in MM patients. Vitamin D deficiency may promote angiogenesis and participate in the occurrence and development of MM by downregulating miR-125b-5p and upregulating HIF-1α and VEGFA expression.