Hsa_circ_0000497 and hsa_circ_0000918 contributed to peritoneal metastasis of ovarian cancer via ascites

Luo, Ning; Sulaiman, Zubaidan; Wang, Chunyan; Ding, Jinye; Chen, Yingying; Liu, Biting; Cheng, Zhongping; Liu, Shupeng

doi:10.1186/s12967-022-03404-9

Cited by 9 publications

(4 citation statements)

References 49 publications

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“…Among the 10 identified DEcircRNAs, hsacirccirc0001947, Circcirc0058058 and hsacirc0004277 have been found to be correlated with AML. [15][16][17][18] Existing research has suggested that hsacirc0001947 inhibits AML cell proliferation via the hsa-miR-329-5p/CREBRF axis. 15 Circ0058058 knockdown accelerated leukocytes apoptosis and inhibited AML progression by targeting miR-4319 to down-regulated EIF5A2 expression, and circ0058058 was considered a possible therapeutic target for AML.…”

Section: Discussionmentioning

confidence: 99%

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Construction of circRNA–miRNA–mRNA Network Reveal Functional circRNAs and Key Genes in Acute Myeloid Leukemia

Hu¹,

Zheng²,

Yang³

et al. 2023

IJGM

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Introduction:CircRNA is closely correlated with a wide variety of processes of acute myeloid leukemia (AML), whereas the novel circRNAs, their molecular mechanism and the specific function they played in AML should be explored in depth. Methods:The microarray chip data of AML patients and normal samples in the Gene Expression Omnibus (GEO) database were selected to differentially expressed (DE) circRNA, miRNA, and mRNA genes. The miRNA gene was the intersection of the circRNA target gene predicted using CSCD and the miRNA gene screened from AML patients, while the mRNA gene was the intersection of the target gene mRNA of miRNA predicted using miRanda and miRTarBase software and the mRNA gene screened from AML patients. The hub mRNAs related to survival were further screened through Cox proportional hazard regression. CircRNA/miRNA/ mRNA interaction network was constructed by using Cytoscape software.10 circRNAs and 6 miRNAs in bone marrow mononuclear cells (BMMNCs) of AML patients (n=43) and healthy controls (n=35) were determined by RT-qPCR. Correlations between them were analyzed by Pearson correlation coefficient. Results: 10 circRNAs, 6 miRNAs, and 33 mRNAs were identified. Subsequently, the network of circRNAs, miRNAs, and hub genes was built using Cystoscope. Four key circRNAs, seven hub genes and their regulatory pathways were identified. The result of RT-qPCRs showed that hsa_circ_0009581 and hsa_circ_0005273 were significantly upregulated in AML patients while hsa_circ_0000497 and hsa_circ_0001947 were significantly downregulated. Hsa-miR-150-5p was significantly downregulated; hsa-miR-454-3p was upregulated in AML patients. Hsa_circ_0009581 and hsa-miR-150-5p; hsa_ circ_0001947 and hsa-miR-454-3p were inversely correlated using Pearson's correlation coefficient. Conclusion:This study suggests that differentially expressed circRNAs take on a critical significance to AML development and may be the effective therapeutic targets. We suppose that hsa_circ_0009581 promotes leukemia development through hsa-miR-150-5p and hsa_circ_0001947 through hsa-miR-454-3p. hsa_circ_0001947 and hsa_circ_0009581 may provide new directions in the pathogenesis of AML.

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Section: Discussionmentioning

confidence: 99%

“…hsacirc0000497 can promote peritoneal metastasis of ovarian cancer by regulating epithelial-mesenchymal transition (EMT) in vitro. 18 The remaining six circRNAs have not been found to be correlated with tumors.…”

Section: Discussionmentioning

confidence: 99%

Construction of circRNA–miRNA–mRNA Network Reveal Functional circRNAs and Key Genes in Acute Myeloid Leukemia

Hu¹,

Zheng²,

Yang³

et al. 2023

IJGM

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“…The study was performed in accordance with the Declaration of Helsinki and was approved by the institutional ethics committee at Shanghai Tenth People’s Hospital. The mRNA expression data of ovarian cancer were obtained from The Cancer Genome Atlas (TCGA) database ( https://portal.gdc.cancer.gov/ ) and our previous study [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

MUC16 stimulates neutrophils to an inflammatory and immunosuppressive phenotype in ovarian cancer

Wu,

Liu,

Xie

et al. 2023

J Ovarian Res

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Background MUC16 (CA125) is a commonly used tumor marker for ovarian cancer screening and reported to be an immunosuppressive factor by acting on the sialic acid-binding immunoglobulin-like lectin-9 (Siglec-9) on the surface of natural killer cells (NK cells), B cells, and monocytes. However, the role of MUC16 on neutrophils in the tumor microenvironment remains to be further explored. Methods The correlation between the proportion and count of peripheral blood cells, serum inflammatory-related factors and serum MUC16 (CA125) level in patients was constructed based on clinical samples. RNAseq data was obtained from TCGA and sequencing of ovarian cancer tissues, followed by TIMER immune cell infiltration and correlation analysis. Ovarian cancer organoid was constructed to stimulate neutrophils with immunophenotype identification by qPCR and flow cytometry. MUC16 protein stimulation to neutrophils validated the role of MUC16 under the analysis of RNA sequencing and inhibition of NK cytotoxicity in vitro. Results The serum MUC16 level was positively correlated with the proportion and count of peripheral blood neutrophils, neutrophil-to-lymphocyte ratio (NLR) and inflammatory factors IL-6, IL-8, IL-10 and IL-2R. Siglec-9, the receptor of MUC16, was expressed on neutrophils and was positively correlated to neutrophil infiltration in ovarian cancer. After the stimulation of ovarian cancer organoids and MUC16 respectively, the proportions of CD11b+, CD66b+, and ICAM-1+ neutrophils were significantly increased, while the proportion of CXCR4+ neutrophils was slightly decreased, with increasing of of inflammatory factors MMP9, IL-8, OSM, IL-1β, TNF-α, CXCL3, and ROS. RNA-sequencing analysis revealed that inflammatory response, TNFA signaling pathway, and IL6-related pathway were upregulated in MUC16-stimulated neutrophils, accompanied by high expression of immunosuppression-related factors HHLA2, IL-6, TNFRSF9, ADORA2A, CD274 (PD-L1), and IDO1. NK cytotoxicity was decreased when treated by supernanant of MUC16-stimulated neutrophils in vitro. Conclusion MUC16 acted on neutrophils by Siglec-9 leading to an inflammatory and immunosuppressive phenotype in ovarian cancer.

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“…Transcriptomic analyses revealed that the ASCs exhibited mesenchymal phenotypes while the tumor cells from primary and metastatic lesions displayed gene expression patterns of epithelial cells. In vitro studies showed that these two circRNAs promoted migration and invasion, downregulated ZO1 and E-cadherin, and upregulated N-cadherin and vimentin in EOC cells [ 161 ], suggesting that the circRNAs may contribute to EOC metastasis by modulating EMT. However, the therapeutic potential of these circRNAs remains to be evaluated in vivo.…”

Section: Circrnas As Potential Therapeutic Targetsmentioning

confidence: 99%

Circular RNAs in Epithelial Ovarian Cancer: From Biomarkers to Therapeutic Targets

Qiu

Chen

Agbede

et al. 2022

Cancers

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Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer, and more than 70% of patients are diagnosed at advanced stages. Despite the application of surgery and chemotherapy, the prognosis remains poor due to the high relapse rate. It is urgent to identify novel biomarkers and develop novel therapeutic strategies for EOC. Circular RNAs (circRNAs) are a class of noncoding RNAs generated from the “back-splicing” of precursor mRNA. CircRNAs exert their functions via several mechanisms, including acting as miRNA sponges, interacting with proteins, regulating transcription, and encoding functional proteins. Recent studies have identified many circRNAs that are dysregulated in EOC and may be used as diagnostic and prognostic markers. Increasing evidence has revealed that circRNAs play a critical role in ovarian cancer progression by regulating various cellular processes, including proliferation, apoptosis, metastasis, and chemosensitivity. The circRNA-based therapy may be a novel strategy that is worth exploring in the future. Here, we provide an overview of EOC and circRNA biogenesis and functions. We then discuss the dysregulations of circRNAs in EOC and the possibility of using them as diagnostic/prognostic markers. We also summarize the role of circRNAs in regulating ovarian cancer development and speculate their potential as therapeutic targets.

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Hsa_circ_0000497 and hsa_circ_0000918 contributed to peritoneal metastasis of ovarian cancer via ascites

Cited by 9 publications

References 49 publications

Construction of circRNA–miRNA–mRNA Network Reveal Functional circRNAs and Key Genes in Acute Myeloid Leukemia

Construction of circRNA–miRNA–mRNA Network Reveal Functional circRNAs and Key Genes in Acute Myeloid Leukemia

MUC16 stimulates neutrophils to an inflammatory and immunosuppressive phenotype in ovarian cancer

Circular RNAs in Epithelial Ovarian Cancer: From Biomarkers to Therapeutic Targets

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