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Archive > Volume 32 Issue 2 > 2025,32(2):161-168. DOI:10.3872/j.issn.1007-385X.2025.02.004 Prev Next
Basic Research
FOXD2-AS1 regulates the expression of LATS1 through EZH2 to affect the proliferation and migration ability of renal cancer cells
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Abstract:
[Abstract] Objective: To explore the mechanism of lncRNA FOXD2-AS1 regulating the expression of LATS1 via EZH2 to affect the proliferation and migration of clear cell renal cell carcinoma (ccRCC) cells. Methods: The GEPIA 2 online tool was used to analyze the expression levels of FOXD2-AS1 in ccRCC tissues from the Cancer Genome Atlas (TCGA) database, and their correlation with patients’ overall survival rates was evaluated. Quantitative PCR (qPCR) was performed to analyze the expressions of FOXD2-AS1 in renal cancer cells and 26 clinically collected ccRCC tissue samples. CCK-8 cell proliferation assay and transwell chamber migration assay were employed to observe the effects of FOXD2-AS1 knockdown on the proliferation and migration of renal cancer cells. qPCR and Western blot analysis were utilized to assess the impact of FOXD2-AS1 knockdown on the expression of LATS1. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays were performed to analyze the interaction between FOXD2-AS1, EZH2, and LATS1. Results: The GEPIA 2 software analysis revealed that FOXD2-AS1 was significantly upregulated in ccRCC tissues (P < 0.01) and patients with high FOXD2-AS1 expression exhibited lower overall survival rates (P < 0.05). The qPCR analysis results showed that FOXD2-AS1 was significantly upregulated in 26 samples of ccRCC tissues compared with adjacent normal kidney tissues (P < 0.01). Compared with immortalized renal tubular epithelial cell line HK-2, the expression of FOXD2-AS1was significantly elevated in three types of renal cancer cell lines (786-O, ACHN and SN12-PM6) (P < 0.01). Knockdown of FOXD2-AS1 expression significantly decreased the proliferation and migration abilities of renal cancer cells (P < 0.05), and markedly increased the mRNA and protein expression levels of LATS1 (all P < 0.01). RIP and ChIP assays confirmed that FOXD2-AS1 can bind and recruit EZH2 to the promoter region of LATS1 to exert its effect. Salvage experiments demonstrated that knocking down LATS1 or overexpressing EZH2 partially reversed the inhibitory effect of FOXD2-AS1 knockdown on the proliferation and migration of renal cancer cells. Conclusion: FOXD2-AS1 is highly expressed in ccRCC, and it negatively regulates the expression of LATS1 by recruiting EZH2 to the promoter region of the LATS1 gene, thereby facilitating the proliferation and migration of renal cancer cells.
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