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Archive > Volume 32 Issue 2 > 2025,32(2):151-160. DOI:10.3872/j.issn.1007-385X.2025.02.003 Prev Next
Basic Research
Tumor-derived exosomal hsa-miR-29c-3p regulates angiogenesis in cervical squamous cell carcinoma by targeting ATAD2B
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Abstract:
[Abstract] Objective: To investigate the role of SiHa cell-derived exosomal hsa-miR-29c-3p in the angiogenesis of cervical cancer (CC). Methods: Cancer tissue specimens from 45 patients with cervical squamous cell carcinoma (CSCC) and normal cervical tissue specimens from 15 controls were collected from Department of Gynecology, Hengyang Central Hospital from January 2019 to December 2021. CSCC SiHa cells and human umbilical vein endothelial cells （HUVECs）were routinely cultured. miRNA-NC, hsa-miR-29c-3p, si-miRNA-NC, and si-hsa-miR-29c-3p were transfected into SiHa cells with Lipofectamine 2000, grouped as miRNA-NC group, hsa-miR-29c-3p group, si-miRNA-NC group and si-hsa-miR-29c-3p group, respectively. HUVECs were transfected with mimic-NC, miR-29c-3p-mimic, pCMV-NC, and pCMV-ATAD2B (ATPase family protein 2B with AAA domain) using Lipofectamine 2000, grouped as the mimic-NC group, miR-29c-3p-mimic group, pCMV-NC group, pCMV-ATAD2B group, and pCMV-ATAD2B + miR-29c-3p-mimic group. The expression of hsa-miR-29c-3p in CSCC tissues was detected by in situ hybridization (ISH), and CD31-positive blood vessels in CSCC tissues and xenograft tissues were detected by immunohistochemistry (IHC). Exosomes from SiHa and C33a cells were isolated and characterized using transmission electron microscopy (TEM) and western blotting (WB). The uptake of exosomes by HUVECs was examined. The expression of hsa-miR-29c-3p and ATAD2B mRNA in SiHa and C33a cells, as well as in their derived exosomes, was detected using qPCR. Tube-forming assay, Transwell assay, and scratch healing assay were performed to detect the effect of exosomes on the ability of HUVEC migration and tube formation. Dual luciferase reporter gene assay verified the interaction between hsa-miR-29c-3p and ATAD2B. Xenograft experiments examined the effects of SiHa cell-derived exosomes on transplanted tumor growth and angiogenesis in each group. Results: hsa-miR-29c-3p was highly expressed in CSCC tissues and was positively correlated with microvessel density (MVD) (all P < 0.05). Exosomes derived from SiHa and C33a cells exhibited typical exosomal morphology and protein expression patterns. Exosomal hsa-miR-29c-3p from SiHa and C33a cells were efficiently taken up by HUVECs in vitro. The SiHa cell-derived exosomal hsa-miR-29c-3p promoted not only the tube-forming and migration of HUVECs in vitro but also the xenograft growth and angiogenesis in vivo (all P < 0.05). hsa-miR-29c-3p directly targeted ATAD2B and regulated its expression (P < 0.05). Overexpression of ATAD2B reversed the promotive effect of hsa-miR-29c-3p on tube-formation, migration, and scratch-healing in HUVECs (all P < 0.05). Conclusion: SiHa cell-derived exosomal hsa-miR-29c-3p regulates angiogenesis in CSCC tissues by targeting ATAD2B. Exosomal hsa-miR-29c-3p may be a potential diagnostic marker and therapeutic target for CC diagnosis and treatment.
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