Long non-coding RNA ZBTB46-AS1 promotes ovarian cancer progression through regulation of p53 activity by TAF6 protein

OBJECTIVE: To elucidate the oncogenic role and molecular pathways associated with long non-coding RNA ZBTB46-AS1 (lncRNA ZBTB46-AS1) in ovarian cancer (OC) progression. METHODS: Bioinformatics analyses of the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to assess ZBTB46-AS1 expression and prognostic value. Quantitative real-time polymerase chain reaction (qRT-PCR) verified its expression in 22 pairs of OC and adjacent normal tissues, as well as OC cell lines. In vitro functional assays [Cell Counting Kit-8 (CCK8), colony formation, Transwell] and in vivo models [xenograft, lung metastasis] were performed to evaluate the effects of ZBTB46-AS1 knockdown. RNA pull-down, RNA immunoprecipitation (RIP), dual-luciferase reporter, and co-immunoprecipitation (Co-IP) assays clarified its interaction with TATA-box-binding protein-associated factor 6 (TAF6) and tumor suppressor protein p53. RESULTS: ZBTB46-AS1 was significantly upregulated in OC tissues and cell lines, correlating with poor overall survival (OS) of patients. Stable knockdown of ZBTB46-AS1 inhibited the proliferation, colony formation, and epithelial-mesenchymal transition (EMT) of OC cells in vitro, as well as tumor growth and distant metastasis in vivo. Mechanistically, ZBTB46-AS1 directly interacted with TAF6, which attenuated the binding between TAF6 and p53, suppressed p53 transcriptional activity, and consequently downregulated the expression of p21. Notably, co-silencing of ZBTB46-AS1 and p53 effectively reversed the inhibitory effects induced by ZBTB46-AS1 knockdown on OC cell malignant phenotypes. CONCLUSION: ZBTB46-AS1 promotes OC progression via the TAF6-p53 axis, serving as a potential prognostic marker and therapeutic target.