Study on the molecular mechanism of bone marrow mesenchymal stem cells inducing epithelial-mesenchymal transition in HPV-associated cervical cancer through activation of miR-129

Abstract: Background: HPV-associated cervical cancer remains a leading cause of cancer-related death in women worldwide. The role of bone marrow mesenchymal stem cells (BMSCs) and miR-129 in tumor progression remains unclear. Objectives: To investigate miR-129 expression and its clinical significance in HPV-associated cervical cancer and to explore whether BMSCs regulate malignant phenotypes through miR-129. Methods: miR-129 expression was measured by qRT-PCR in 77 cervical cancer and 30 normal cervical tissues. Associations with clinicopathological features and overall survival (OS) were analyzed. Diagnostic value was assessed by ROC curve. Rat BMSCs were co-cultured with SiHa and HeLa cells. Following miR-129 overexpression or knockdown, cell proliferation (CCK-8, colony formation), invasion (Transwell) and expression of E-cadherin, N-cadherin and MRP1 (Western blot) were examined. Results: miR-129 expression was significantly higher in cervical cancer tissues than in normal controls (3.24±0.56 vs. 1.00±0.32, P<0.05). High miR-129 expression correlated with tumor size ≥3 cm (P=0.009), FIGO stage III-IV (P=0.0034) and lymph node metastasis (P=0.038). High expression was associated with shorter OS (median: 28.4 vs. 46.2 months; HR=2.944, 95%CI:1.484-5.842, P=0.002). The AUC was 0.788 (95%CI:0.693-0.884), with a cut-off of 1.85 (sensitivity:76.9%, specificity:70.4%). BMSC co-culture upregulated miR-129 expression (SiHa: 3.52±0.42 vs. 1.00±0.08, P<0.01). miR-129 overexpression promoted proliferation, colony formation and invasion, while knockdown suppressed these phenotypes. Overexpression of miR-129 reduced E-cadherin (0.42±0.05 vs. 1.00±0.08, P<0.01) and increased N-cadherin (2.85±0.22 vs. 1.00±0.10, P<0.01) and MRP1 (2.46±0.18 vs. 1.00±0.09, P<0.01). Knockdown of miR-129 partially reversed BMSC-induced changes in these proteins. Conclusion: miR-129 is significantly upregulated in HPV-associated cervical cancer and shows potential as a diagnostic and prognostic biomarker. BMSCs upregulate miR-129 in cervical cancer cells and miR-129 modulates proliferation, invasion, EMT marker expression and MRP1 expression. These findings suggest that the BMSCs/miR-129 axis may contribute to cervical cancer progression, but further in-vivo and mechanistic studies are needed.