ArticleJournal of experimental & clinical cancer research : CR2019
Long non-coding RNA GAS5 inhibits DDP-resistance and tumor progression of epithelial ovarian cancer via GAS5-E2F4-PARP1-MAPK axis.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 146 citations in OpenAlex.
- Fusobacterium nucleatum regulates nicotinamide metabolism via the upregulation of NNMT to activate PARP1/MAPK signalling in colitis-associated cancer.Cellular and molecular life sciences : CMLS · 2026Article
- Targeting epigenetic networks to overcome cisplatin resistance in ovarian cancer: from mechanisms to clinical translation.Journal of ovarian research · 2026Review
- Recent advances in the role of long non-coding RNAs in ovarian cancer chemoresistance.Journal of ovarian research · 2026Review
- LncRNAs in Ovarian Cancer: Emerging Insights and Future Perspectives in Tumor Biology and Clinical Applications.Cancers · 2026Review
- LncRNAs signatures in gynecological cancers: ovarian and endometrial cancers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- The roles of the small nucleolar RNA host gene family in ovarian cancer.Cancer biology & therapy · 2025Review
- The Role of Non-Coding RNAs in the Regulation of Oncogenic Pathways in Breast and Gynaecological Cancers.Non-coding RNA · 2025Review
- ESM1 suppresses LncRNA GAS5/miR-23a-3p/PTEN axis to promote the cisplatin-chemotherapy resistance of ovarian cancer cells via activating the PI3K/AKT pathway.Discover oncology · 2025Article
- Long Non-Coding RNAs in Ovarian Cancer: Mechanistic Insights and Clinical Applications.Cancers · 2025Review
- The emerging role of circular RNAs in cisplatin resistance in ovarian cancer: From molecular mechanism to future potential.Non-coding RNA research · 2024Review
- The Role of Long Non-Coding RNAs in Ovarian Cancer Cells.International journal of molecular sciences · 2024Review
- GAS5 regulated by FTO-mediated m6A modification suppresses cell proliferation via the IGF2BP2/QKI axis in breast cancer.Discover oncology · 2024Article
- Prognostic Significance of Dual-Specificity Phosphatase 23 Expression in Acute Myeloid Leukemia.Journal of blood medicine · 2024Article
- Novel players in the development of chemoresistance in ovarian cancer: ovarian cancer stem cells, non-coding RNA and nuclear receptors.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Article
- Expression of lncRNAs in children with pancreaticobiliary maljunction: functional analysis and potential biomarkers.Archives of medical science : AMS · 2024Article
- The roles of long non-coding RNAs in ovarian cancer: from functions to therapeutic implications.Frontiers in oncology · 2024Review
- Long non-coding RNA GAS5 promotes cisplatin-chemosensitivity of osteosarcoma cells via microRNA-26b-5p/TP53INP1 axis.Journal of orthopaedic surgery and research · 2023Article
- Role of long non-coding RNAs in cancer: From subcellular localization to nanoparticle-mediated targeted regulation.Molecular therapy. Nucleic acids · 2023Review
- GAS5-inhibited hepatocyte pyroptosis contributes to hepatic stellate cell inactivation via microRNA-684 and AHR.iScience · 2023Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundEpithelial ovarian cancer (EOC) is the malignant tumor of the female reproductive system with the highest fatality rate. Tolerance of chemotherapeutic drugs like cisplatin (DDP) occurring in very early stage is one of the important factors of the poor prognosis of epithelial ovarian cancer. Here we aim to study the dysregulation of a particular long noncoding RNA, lncRNA GAS5, and its role in EOC progression.
methodsThe low expression of lncRNA GAS5 in EOC tissues and OC cell lines was determined by microarray analyses and Real-Time qPCR. Flow cytometer assays were used to detect cell cycle and apoptosis of OC cells. CCK8 assay were performed to investigate the DDP sensitivity of OC cells. Western blot was carried out to detect cell growth markers, apoptotic markers, PARP1, E2F4, MAPK pathway protein expression and other protein expression in OC cell lines. The binding of GAS5 and E2F4 were proved by RNA pull-down and RIP assay. The effect of E2F4 on PARP1 were determined by CHIP-qPCR assay and luciferase reporter assay. The effect of lncRNA GAS5 on OC cells was assessed in vitro and in vivo.
resultsBy microarray (3 EOC tissues νs. 3 normal ovary tissues) and RT- qPCR (53 EOC tissues νs. 10 normal ovary tissues) we identified lncRNA GAS5 to be dramatically low expressed in EOC samples and correlated with prognosis. Compared with sensitive cell lines, GAS5 was also low expressed in DDP resistant OC cell lines, and over-expression of GAS5 significantly enhanced the sensitivity of OC cells to DDP in vivo and in vitro. Meanwhile the over-expression of GAS5 also caused OC cells G0/G1 arrest and apoptosis increase. Mechanistically, GAS5 might regulate PARP1 expression by recruiting the transcription factor E2F4 to its promoter, and then affect the MAPK pathway activity. Due to the 5'TOP structure, GAS5 could be regulated by transcription inhibitor rapamycin in OC cells.
conclusionHere we explored the specific mechanisms of EOC cisplatin resistance and tumor progress due to lncRNA-GAS5, presented the GAS5-E2F4-PARP1-MAPK axis and its role in OC drug-sensitivity and progression for the first time, and the results may provide experimental basis for clinical application.
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