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Archive > Volume 32 Issue 10 > 2025,32(10):1036-1043. DOI:10.3872/j.issn.1007-385X.2025.10.005 Prev Next
Basic Research
Effects of RBM15 on the proliferation, migration and invasion of cervical cancer cells by regulating the Wnt/β-catenin pathway through ATAD3A
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Abstract:
[Abstract] Objective: To investigate the effects of RNA binding protein 15 (RBM15) on the malignant biological behaviors of cervical cancer cells by regulating the Wnt/β-catenin pathway through ATPase family AAA-domain containing 3A (ATAD3A). Methods: TCGA database was used to analyze the expression level of RBM15 mRNA in cervical cancer tissues and its relationship with patient prognosis. 32 samples of cervical cancer tissues and adjacent para-cancerous tissues surgically removed in Ganzhou People's Hospital between January and October 2024, as well as cervical cancer cells HeLa, MS-751, C-33A, and SiHa, were collected. The expression levels of RBM15 in cervical cancer tissues and cells were detected by immunohistochemistry and WB assay. m6 A modification sites in ATAD3A mRNA were screened by the SRAMP online database. The interaction between RBM15 and ATAD3A mRNA were identified by RNA immunoprecipitation assay, RNA decay assay, and salvage assay. Knockdown or overexpression of RBM15 and ATAD3A in cervical cancer HeLa and SiHa cells were conducted by RNA interference and viral infection. The expressions of mRNA and protein were detected by qPCR and WB methods, while the proliferation, migration, and invasion abilities of cells in each group were assessed by CCK-8 method, scratch assay, and Transwell assay. Results: The positivity rates of RBM15 mRNA and protein in cervical cancer tissues were significantly higher than those in adjacent para-cancerous tissues (both P < 0.001). The protein expression levels of RBM15 in cervical cancer cell lines HeLa, MS-751, C-33A, and SiHa were significantly higher than those in normal cervical cell lines Ect1/E6E7 (all P < 0.001). The 5-year progression free survival rate of the RBM15 mRNA high expression group was lower than that of the low expression group (P < 0.001). Compared with that in adjacent para-cancerous tissues, the expression level of ATAD3A was significantly upregulated in cervical cancer tissues (P < 0.001). RBM15 mRNA was positively correlated with ATAD3A mRNA (r = 0.601, P < 0.05). There were highly reliable m6 A modification sites at position 501, 5 312, 12 137 in ATAD3A mRNA. Overexpression of RBM15 in HeLa and SiHa cells led to an increase in ATAD3A mRNA and protein expressions, while knockdown of RBM15 resulted in a decrease in ATAD3A mRNA and protein expression (all P < 0.001). RNA immunoprecipitation experiment showed that compared with the IgG group, ATAD3A mRNA was significantly enriched in the immunoprecipitation of RBM15 antibody (both P < 0.001). MeRIP-qPCR experiment showed that there was significant m6 A methylation enrichment at positions ATAD3A mRNA 501, 5 312 and 12 137 (all P < 0.001). RNA decay experiments showed that knocking down RBM15 in HeLa and SiHa cells could reduce the half-life and stability of ATAD3A mRNA (all P < 0.001). Knocking down the expression of RBM15 in HeLa and SiHa cells could significantly inhibit the proliferation, migration, and invasion of cancer cells and significantly reduce the expressions of Wnt/β-catenin pathway related proteins Wnt3, β-catenin, and vimentin, while overexpression of ATAD3A could completely reverse the above inhibiting effects (all P < 0.001). Conclusion: RBM15 can modify ATAD3A mRNA and regulate the Wnt/β-catenin pathway through m6 A, and thus promote the proliferation, migration and invasion of cervical cancer cells.
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