ETV5-mediated upregulation of lncRNA CTBP1-DT as a ceRNA facilitates HGSOC progression by regulating miR-188-5p/MAP3K3 axis

Liu, Ping; Fu, Ruiting; Chen, Kai; Zhang, Lu; Wang, Shasha; Liang, Wei; Zou, Hong; Lin, Tao; Jia, Wei Hua

doi:10.1038/s41419-021-04256-9

Cited by 11 publications

(12 citation statements)

References 38 publications

(39 reference statements)

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“…For example, inhibition of HOXD-AS1 reduced OC cell migration, invasion, and epithelial-mesenchymal transition (EMT) in OC cells in vitro by preventing HOXD-AS1 directly binding to miR-186-5p, and resulting in down-regulating of PIK3R3 [ 21 ]. Overexpression of lncRNA CTBP1-DT could competitively bind to miR-188-5p to protect MAP3K3 from degradation, which could promote malignant biological behaviors of HGSOC (high-grade serous ovarian cancer) cells [ 22 ]. To accurately predict the clinical outcomes or chemotherapy resistance of OC patients and improve their long-term survival, the development of novel molecular biomarkers for early OC detection is a high priority [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Development and verification of a 7-lncRNA prognostic model based on tumor immunity for patients with ovarian cancer

Feng

Yu²,

Yin³

et al. 2023

J Ovarian Res

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Background Both immune-reaction and lncRNAs play significant roles in the proliferation, invasion, and metastasis of ovarian cancer (OC). In this study, we aimed to construct an immune-related lncRNA risk model for patients with OC. Method Single sample GSEA (ssGSEA) algorithm was used to analyze the proportion of immune cells in The Cancer Genome Atlas (TCGA) and the hclust algorithm was used to conduct immune typing according to the proportion of immune cells for OC patients. The stromal and immune scores were computed utilizing the ESTIMATE algorithm. Weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) analyses were utilized to detect immune cluster-related lncRNAs. The least absolute shrinkage and selection operator (LASSO) regression was conducted for lncRNA selection. The selected lncRNAs were used to construct a prognosis-related risk model, which was then validated in Gene Expression Omnibus (GEO) database and in vitro validation. Results We identify two subtypes based on the ssGSEA analysis, high immunity cluster (immunity_H) and low immunity cluster (immunity_L). The proportion of patients in immunity_H cluster was significantly higher than that in immunity_L cluster. The ESTIMATE related scores are relative high in immunity_H group. Through WGCNA and LASSO analyses, we identified 141 immune cluster-related lncRNAs and found that these genes were mainly enriched in autophagy. A signature consisting of 7 lncRNAs, including AL391832.3, LINC00892, LINC02207, LINC02416, PSMB8.AS1, AC078788.1 and AC104971.3, were selected as the basis for classifying patients into high- and low-risk groups. Survival analysis and area under the ROC curve (AUC) of the signature pointed out that this risk model had high accuracy in predicting the prognosis of patients with OC. We also conducted the drug sensitive prediction and found that rapamycin outperformed in patient with high risk score. In vitro experiments also confirmed our prediction. Conclusions We identified 7 immune-related prognostic lncRNAs that effectively predicted survival in OC patients. These findings may offer a valuable indicator for clinical stratification management and personalized therapeutic options for these patients.

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Section: Discussionmentioning

confidence: 99%

Development and verification of a 7-lncRNA prognostic model based on tumor immunity for patients with ovarian cancer

Feng

Yu²,

Yin³

et al. 2023

J Ovarian Res

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“…Therefore, ovarian cancer is characterized by increased expression of epithelial markers rather than following the classical model of the EMT, the process of which is different from other epithelial tumors. In ovarian cancer, ETV5 was found to promote cell proliferation, migration and invasion through the regulation of lncRNA CTBP1-DT [ 139 ]. Cancer cells with downregulated ETV5 exhibited reduced adhesion to collagen type I, collagen type IV, fibronectin, and laminin [ 140 ].…”

Section: Etv5 In Cancer Biologymentioning

confidence: 99%

E26 transformation-specific transcription variant 5 in development and cancer: modification, regulation and function

et al. 2023

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E26 transformation-specific (ETS) transcription variant 5 (ETV5), also known as ETS-related molecule (ERM), exerts versatile functions in normal physiological processes, including branching morphogenesis, neural system development, fertility, embryonic development, immune regulation, and cell metabolism. In addition, ETV5 is repeatedly found to be overexpressed in multiple malignant tumors, where it is involved in cancer progression as an oncogenic transcription factor. Its roles in cancer metastasis, proliferation, oxidative stress response and drug resistance indicate that it is a potential prognostic biomarker, as well as a therapeutic target for cancer treatment. Post-translational modifications, gene fusion events, sophisticated cellular signaling crosstalk and non-coding RNAs contribute to the dysregulation and abnormal activities of ETV5. However, few studies to date systematically summarized the role and molecular mechanisms of ETV5 in benign diseases and in oncogenic progression. In this review, we specify the molecular structure and post-translational modifications of ETV5. In addition, its critical roles in benign and malignant diseases are summarized to draw a panorama for specialists and clinicians. The updated molecular mechanisms of ETV5 in cancer biology and tumor progression are delineated. Finally, we prospect the further direction of ETV5 research in oncology and its potential translational applications in the clinic.

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“…To date, regardless of the continuous improvement and development of surgical and systematic management, the mortality of these patients has not been improved under the standard regimens with approximately 70% of patients having relapse and metastasis after treatment. Consequently, identifying the mechanisms that drive HGSOC metastasis will translate into clinical managements that would improve their outcomes (1,(5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

“…Ovarian cancer (OC) is the 7 th most commonly diagnosed gynecologic malignancy worldwide, accounting for 2.5% of all female cancers ( 1 , 2 ). In 2020, there were about 313,959 new cases and 207,252 deaths of OC worldwide in the world ( 3 , 4 ).…”

Section: Introductionmentioning

confidence: 99%

“…OC is a heterogeneous disease that is histologically classified into 5 major subtypes: high-grade serous, low-grade serous, clear cell carcinoma, endometrioid carcinoma, and mucinous ovarian carcinoma ( 3 , 4 ). High-grade serous ovarian cancer (HGSOC) is the most common histological subtype of OC and accounts for 67.5% of all OC subtypes ( 1 , 2 ), and remains the most lethal female cancer with an estimated 21,410 new cases and 13,770 deaths expected in the United States in 2021 ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive analysis of m6A-modified circRNAs in peritoneal metastasis of high grade serious carcinoma of ovary

Guo

Xu²,

Qiu³

et al. 2022

Front. Oncol.

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PurposeHigh-grade serous ovarian cancer (HGSOC) remains the most lethal female cancer due to metastasis. CircRNAs are recently identified to be modified by N6-methyladenosine (m6A) in many cells. However, the significance of m6A-modified circular RNAs (circRNAs) has not been elucidated in HGSOC peritoneal metastasis. Here, we aimed to investigate the participation and potential functions of m6A-modified circRNAs in HGSCO peritoneal metastasis.MethodsCancerous tissues were collected from the in situ and the peritoneal metastasis lesions of HGSCO patients. M6A-tagged circRNAs were identified by m6A-modified RNA immunoprecipitation sequencing (m6A-RIP-seq). Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict the potential functions of the m6A-modified circRNAs.ResultsFor the m6A-modified circRNAs, 259 were upregulated and 227 were downregulated in the peritoneal metastasis than in the situ lesions of HGSCO patients. For the m6A peaks, 1541 were upregulated and 1293 were downregulated in the peritoneal metastasis than in the in situ lesions of HGSCO patients. For the differential expressed circRNAs, 1911(19.6%) were upregulated and 2883(29.6%) were downregulated in the peritoneal metastasis than in the in situ lesions of HGSCO patients. The upregulated m6A-modified circRNAs were associated with the HIF-1 signaling. The downregulated m6A-modified circRNAs were associated with the MAPK signaling.ConclusionsThis work firstly identified the transcriptome-wide map of m6A-modified circRNAs in peritoneal metastasis of HGSCO. Our findings provided novel evidences about the participation of m6A-modified circRNAs via HIF-1 and MAPK signaling and a new insight in molecular target of HGSCO peritoneal metastasis.

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ETV5-mediated upregulation of lncRNA CTBP1-DT as a ceRNA facilitates HGSOC progression by regulating miR-188-5p/MAP3K3 axis

Cited by 11 publications

References 38 publications

Development and verification of a 7-lncRNA prognostic model based on tumor immunity for patients with ovarian cancer

Development and verification of a 7-lncRNA prognostic model based on tumor immunity for patients with ovarian cancer

E26 transformation-specific transcription variant 5 in development and cancer: modification, regulation and function

Comprehensive analysis of m6A-modified circRNAs in peritoneal metastasis of high grade serious carcinoma of ovary

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