ArticleCell death & disease2024
CSTF3 contributes to platinum resistance in ovarian cancer through alternative polyadenylation of lncRNA NEAT1 and generating the short isoform NEAT1_1.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- INHBA secreted by cancer-associated fibroblasts promotes cisplatin resistance and malignant progression of ovarian cancer via ENG-mediated suppression of apoptosis and induction of EMT.Journal of translational medicine · 2026Article
- NEAT1: a multifaceted long non-coding RNA in multiple myeloma.Haematologica · 2026Review
- Deconstructing the RAGE signaling maze: the molecular key to opening a new dimension of ovarian anti-aging.Experimental & molecular medicine · 2026Review
- ALKBH5 Accelerates the Progression of Head and Neck Squamous Cell Carcinoma by Decreasing Methylation of the lncRNA NEAT1.Applied biochemistry and biotechnology · 2026Article
- The Oncogenic Role of Long Non-Coding RNABiology · 2026Review
- LncRNAs in Ovarian Cancer: Emerging Insights and Future Perspectives in Tumor Biology and Clinical Applications.Cancers · 2026Review
- Insights into organelle forming RNAs: Diversity, functions and future perspectives.Animal models and experimental medicine · 2025Review
- Article
- Functional characterization of dysregulated LncRNAs in BRCA and CESC highlights their role in cancer prognosis.Scientific reports · 2025Article
- Article
- [Layered double hydroxide-loaded si-NEAT1 regulates paclitaxel resistance and tumor-associated macrophage polarization in breast cancer by targeting miR-133b/PD-L1].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- IGF2BP2 binding to CPSF6 facilitates m6A-mediated alternative polyadenylation of PUM2 and promotes malignant progression in ovarian cancer.Clinical and translational medicine · 2025Article
- IGF2BP3 recruits NUDT21 to regulate SPTBN1 alternative polyadenylation and drive ovarian cancer progression.Communications biology · 2025Article
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- Knockdown of TOP2A reverses cisplatin resistance in ovarian cancer by inhibiting EMT via ferroptosis mediated by the TP53/GPX4/SLC7A11 axis.Frontiers in immunology · 2025Article
- Identifying the ceRNA Regulatory Network in Early-Stage Acute Pancreatitis and Investigating the Therapeutic Potential of NEAT1 in Mouse Models.Journal of inflammation research · 2024Article
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13 authors.
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Abstract
Platinum-based chemotherapy is the standard postoperative adjuvant treatment for ovarian cancer (OC). Despite the initial response to chemotherapy, 85% of advanced OC patients will have recurrent disease. Relapsed disease and platinum resistance are the major causes of death in OC patients. In this study, we compared the global regulation of alternative polyadenylation (APA) in platinum-resistant and platinum-sensitive tissues of OC patients by analyzing a set of single-cell RNA sequencing (scRNA-seq) data from public databases and found that platinum-resistant patients exhibited global 3' untranslated region (UTR) shortening due to the different usage of polyadenylation sites (PASs). The APA regulator CSTF3 was the most significantly upregulated gene in epithelial cells of platinum-resistant OC. CSTF3 knockdown increased the sensitivity of OC cells to platinum. The lncRNA NEAT1 has two isoforms, short (NEAT1_1) and long (NEAT1_2) transcript, because of the APA processing in 3'UTR. We found that CSTF3 knockdown reduced the usage of NEAT1 proximal PAS to lengthen the transcript and facilitate the expression of NEAT1_2. Downregulation of the expression of NEAT1 (NEAT1_1/_2), but not only NEAT1_2, also increased the sensitivity of OC cells to platinum. Overexpressed NEAT1_1 reversed the platinum resistance of OC cells after knocking down CSTF3 expression. Furthermore, downregulated expression of CSTF3 and NEAT1_1, rather than NEAT1_2, was positively correlated with inactivation of the PI3K/AKT/mTOR pathway in OC cells. Together, our findings revealed a novel mechanism of APA regulation in platinum-resistant OC. CSTF3 directly bound downstream of the NEAT1 proximal PAS to generate the short isoform NEAT1_1 and was conducive to platinum resistance, which provides a potential biomarker and therapeutic strategy for platinum-resistant OC patients.
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