Global characterization of extrachromosomal circular DNAs in advanced high grade serous ovarian cancer

Cen, Yixuan; Fang, Yifeng; Ren, Yan; Hong, Siqi; Lü, Weiguo; Xu, Jianrong

doi:10.1038/s41419-022-04807-8

Cited by 36 publications

(38 citation statements)

References 42 publications

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“… 25 , 28 , 275 , 276 Several studies have demonstrated the potential application of extrachromosomal DNA elements in body fluids as candidate biomarkers for the diagnosis and monitoring of various diseases (Table 4 ). 81 , 277 , 278 …”

Section: Potential Applications Of Eccdnamentioning

confidence: 99%

Extrachromosomal circular DNA: biogenesis, structure, functions and diseases

Yang

Jia

et al. 2022

Sig Transduct Target Ther

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Extrachromosomal circular DNA (eccDNA), ranging in size from tens to millions of base pairs, is independent of conventional chromosomes. Recently, eccDNAs have been considered an unanticipated major source of somatic rearrangements, contributing to genomic remodeling through chimeric circularization and reintegration of circular DNA into the linear genome. In addition, the origin of eccDNA is considered to be associated with essential chromatin-related events, including the formation of super-enhancers and DNA repair machineries. Moreover, our understanding of the properties and functions of eccDNA has continuously and greatly expanded. Emerging investigations demonstrate that eccDNAs serve as multifunctional molecules in various organisms during diversified biological processes, such as epigenetic remodeling, telomere trimming, and the regulation of canonical signaling pathways. Importantly, its special distribution potentiates eccDNA as a measurable biomarker in many diseases, especially cancers. The loss of eccDNA homeostasis facilitates tumor initiation, malignant progression, and heterogeneous evolution in many cancers. An in-depth understanding of eccDNA provides novel insights for precision cancer treatment. In this review, we summarized the discovery history of eccDNA, discussed the biogenesis, characteristics, and functions of eccDNA. Moreover, we emphasized the role of eccDNA during tumor pathogenesis and malignant evolution. Therapeutically, we summarized potential clinical applications that target aberrant eccDNA in multiple diseases.

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Section: Potential Applications Of Eccdnamentioning

confidence: 99%

Extrachromosomal circular DNA: biogenesis, structure, functions and diseases

Yang

Jia

et al. 2022

Sig Transduct Target Ther

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“…For the migration experiments, treated SKOV3 and 3AO cells (1 × 10 [ 5 ] cells/well) were seeded in the upper chambers of 24-well plates (pore size, 8.0 μm; BD, USA). The medium in the chamber was serum-free, whereas the medium in the lower chambers contained 10% fetal bovine serum.…”

Section: Methodsmentioning

confidence: 99%

“…Among these, serous cancers are the most prevalent [ 3 ]. Therefore, it is important to understand the organizational structure of EOC [ 4 , 5 ], its occurrence and development [ 6 ], and its drug resistance mechanisms [ 7 ]. Moreover, it is important to seek suitable biological targets [ 8 ] and treatments [ 9 , 10 ] for this cancer.…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA SLC25A21-AS1 inhibits the development of epithelial ovarian cancer by specifically inducing PTBP3 degradation

Shen

et al. 2023

Biomark Res

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Background Epithelial ovarian cancer (EOC) is a highly prevalent disease that rapidly metastasizes and has poor prognosis. Most women are in the middle or late stages when diagnosed and have low survival rates. Recently, long non-coding RNAs (lncRNAs) were recognized to play pivotal roles in the development of EOC. Methods The expression of SLC25A21 antisense RNA 1 (SLC25A21-AS1) and Polypyrimidine Tract Binding Protein 3 (PTBP3) in EOC cells was assessed via qPCR. The proliferation activity of these cells was detected by EdU and Cell counting kit-8 (CCK8) assays, while the death rate of apoptotic cells and the cell cycle were detected by flow cytometry. Detection of cell transfer rate by transwell assay. Protein expression was measured through western blotting. Interactions between SLC25A21-AS1 and PTBP3 were detected through RNA immunoprecipitation (RIP), IF-FISH co-localization experiments and electrophoretic mobility shift assay (EMSA). The in vivo importance of SLC25A21-AS1 as a tumor suppressor modulator was assessed using murine xenograft models. Results The lncRNA SLC25A21-AS1 has negligible expression in ovarian cancer tissues compared with that in normal ovarian tissues. A series of functional experiments revealed that the upregulation of SLC25A21-AS1 markedly blocked the proliferation and metastasis of EOC cells in vitro, while its downregulation had the opposite effect. Overexpression of SLC25A21-AS1 in a nude mouse model of EOC in vivo resulted in slower tumor growth and weakened metastatic potential. Moreover, SLC25A21-AS1 reduced the protein stability of PTBP3 and promoted its degradation. A series of subsequent experiments found that SLC25A21-AS1 inhibits EOC cell proliferation and metastasis by modulating PTBP3 through the ubiquitin-proteasome pathway and that the combination of SLC25A21-AS1 and PTBP3 provides the necessary conditions for the for the function to be realized. Conclusions Our research reveals the effect of SLC25A21-AS1 in EOC development and suggests SLC25A21-AS1 can serve as a prognostic target by promoting the degradation of PTBP3 to improve patient survival.

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“…Currently, the standard treatment for OC is surgery combined with chemotherapy. Despite this, the 5-year survival rate of the patients is only 45% [ 3 ]. However, the pathogenesis of OC is not yet fully defined.…”

Section: Introductionmentioning

confidence: 99%

NUF2 promotes tumorigenesis by interacting with HNRNPA2B1 via PI3K/AKT/mTOR pathway in ovarian cancer

et al. 2023

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Background Ovarian cancer (OC) is one of the commonest and deadliest diseases that threaten the health of women worldwide. It is essential to find out its pathogenic mechanisms and therapeutic targets for OC patients. Although NUF2 (Ndc80 kinetochore complex component) has been suggested to play an important role in the development of many cancers, but little is known about its function and the roles of proteins that regulate NUF2 in OC. This study aimed to investigate the effect of NUF2 on the tumorigenicity of OC and the activities of proteins that interact with NUF2. Methods Oncomine database and immunohistochemical (IHC) staining were used to evaluate the expression of NUF2 in OC tissues and normal tissues respectively. Normal ovarian epithelial cell lines (HOSEpiC) and OC cell lines (OVCAR3、HEY、SKOV3) were cultured. Western blot was applied to analyze the expression of NUF2 in these cell lines. Small interfering RNA (siRNA) was used to silence the expression of NUF2 in OC cell lines, SKOV3 and HEY. Gene Set Variation Analysis (GSVA), Gene Set Enrichment Analysis (GSEA), the CCK-8 method, colony formation assay and flow cytometry were conducted to analyze the biological functions of NUF2 in vitro. OC subcutaneous xenograft tumor models were used for in vivo tests. Immunoprecipitation and mass spectrometry (IP/MS) were performed to verify the molecular mechanisms of NUF2 in OC. IP, immunofluorescence, IHC staining, and Gene Expression Profiling Interactive Analysis platform (GEPIA) were used to analyze the relationship between HNRNPA2B1 and NUF2 in OC cells. SiRNA was used to silence the expression of HNRNPA2B1 in SKOV3 cells, reverse transcription quantitative polymerase chain reaction (RT-qPCR) assay and western blot were used to detect the effect of HNRNPA2B1 on NUF2. GEPIA, The Cancer Genome Atlas (TCGA) database, GSEA and western blot were used to detect the potential signaling pathways related to the roles of HNRNPA2B1 and NUF2 in OC cells. Results Our results showed high NUF2 expression in OC tissues and OC cell lines, which was associated with shorter overall survival and progression-free survival in patients. NUF2 depletion by siRNA suppressed the proliferation abilities and induced cell apoptosis of OC cells in vitro, and impeded OC growth in vivo. Mechanistically, NUF2 interacted with HNRNPA2B1 and activated the PI3K/AKT/mTOR signaling pathway in OC cells. Conclusion NUF2 could serve as a prognostic biomarker, and regulated the carcinogenesis and progression of OC. Moreover, NUF2 may interact with HNRNPA2B1 by activating the PI3K/AKT/mTOR signaling pathway to promote the development of OC cells. Our present study supported the key role of NUF2 in OC and suggested its potential as a novel therapeutic target.

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Global characterization of extrachromosomal circular DNAs in advanced high grade serous ovarian cancer

Cited by 36 publications

References 42 publications

Extrachromosomal circular DNA: biogenesis, structure, functions and diseases

Extrachromosomal circular DNA: biogenesis, structure, functions and diseases

Long non-coding RNA SLC25A21-AS1 inhibits the development of epithelial ovarian cancer by specifically inducing PTBP3 degradation

NUF2 promotes tumorigenesis by interacting with HNRNPA2B1 via PI3K/AKT/mTOR pathway in ovarian cancer

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