FoxP3-miR-150-5p/3p suppresses ovarian tumorigenesis via an IGF1R/IRS1 pathway feedback loop

Zhang, Qinkai; Zhou, Xunzhu; Wan, Maoping; Zeng, Xixi; Luo, Junhua; Xu, Yesha; Ji, Liying; Zhang, Jianan; Fan, Pei; Zhong, Jianing; Wu, Jianmin

doi:10.1038/s41419-021-03554-6

Cited by 20 publications

(17 citation statements)

References 74 publications

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“…It has been suggested that miR-150 may play a role in various types of tumor development. It is also associated with the regulation of ovarian cancer and the poor prognosis of NSCLC patients [ 41 , 42 ]. In the case of breast cancer, miR-150 is regulated by lncRNA MAFG-AS1.…”

Section: Discussionmentioning

confidence: 99%

CASC1 Expression in Bladder Cancer Is Regulated by Exosomal miRNA-150: A Comprehensive Pan-Cancer and Bioinformatics Study

Luo

et al. 2022

Computational and Mathematical Methods in Medicine

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This study explored the role of cancer susceptibility 1 (CASC1) in tumorigenesis and development as well as the key pathways affecting bladder cancer progression. CASC1 was examined in various normal tissues in humans using the HPA database to quantify its expression level and subcellular localization. CASC1 is abundantly expressed in tumor tissues, primarily in cytoplasmic vesicles and stroma. TIMER2 was used to analyze the correlation between CASC1 expression levels and the types of infiltrates associated with immune cells and immunosuppressive cells. MDSC, Treg, M2, and CAF were significantly correlated with CASC1 expression in various tumors. Comparing patients with and without CASC1 mutation, those with CASC1 mutation had worse overall survival, progression-free survival, and disease-free survival. The correlation between has-miR-150 and CASC1 (for the case of bladder cancer) was then analyzed, and the related ceRNA network was mapped. A negative relationship between CASC1 expression and has-miR-150 expression was found in cases of bladder cancer. And the presence of miR-150-targeted CASC1 may be associated with bladder cancer progression. CASC1 is expressed at elevated levels in various tumor tissues, and it is associated with tumorigenesis and development. Exosomes containing miR-150-targeted CASC1 may affect the progression of bladder cancer.

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Section: Discussionmentioning

confidence: 99%

CASC1 Expression in Bladder Cancer Is Regulated by Exosomal miRNA-150: A Comprehensive Pan-Cancer and Bioinformatics Study

Luo

et al. 2022

Computational and Mathematical Methods in Medicine

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“…Among the most significant 10 pathways, five were signal transduction pathways, including the MAPK signaling pathway, AMPK signaling pathway, PI3K-Akt signaling pathway, Estrogen signaling pathway, and Hippo signaling pathway. In particular, the PI3K/AKT/mTOR cascade has been identified as frequently altered in OVC ( 22 ). The three signaling pathways were all significantly disturbed by the diagnostic miRNAs, implying their important role in OVC.…”

Section: Resultsmentioning

confidence: 99%

Predict ovarian cancer by pairing serum miRNAs: Construct of single sample classifiers

et al. 2022

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ObjectiveThe accuracy of CA125 or clinical examination in ovarian cancer (OVC) screening is still facing challenges. Serum miRNAs have been considered as promising biomarkers for clinical applications. Here, we propose a single sample classifier (SSC) method based on within-sample relative expression orderings (REOs) of serum miRNAs for OVC diagnosis.MethodsBased on the stable REOs within 4,965 non-cancer serum samples, we developed the SSC for OVC in the training cohort (GSE106817: OVC = 200, non-cancer = 2,000) by focusing on highly reversed REOs within OVC. The best diagnosis is achieved using a combination of reversed miRNA pairs, considering the largest evaluation index and the lowest number of miRNA pairs possessed according to the voting rule. The SSC was then validated in internal data (GSE106817: OVC = 120, non-cancer = 759) and external data (GSE113486: OVC = 40, non-cancer = 100).ResultsThe obtained 13-miRPairs classifier showed high diagnostic accuracy on distinguishing OVC from non-cancer controls in the training set (sensitivity = 98.00%, specificity = 99.60%), which was reproducible in internal data (sensitivity = 98.33%, specificity = 99.21%) and external data (sensitivity = 97.50%, specificity = 100%). Compared with the published models, it stood out in terms of correct positive predictive value (PPV) and negative predictive value (NPV) (PPV = 96.08% and NPV=95.16% in training set, and both above 99% in validation set). In addition, 13-miRPairs demonstrated a classification accuracy of over 97.5% for stage I OVC samples. By integrating other non-OVC serum samples as a control, the obtained 17-miRPairs classifier could distinguish OVC from other cancers (AUC>92% in training and validation set).ConclusionThe REO-based SSCs performed well in predicting OVC (including early samples) and distinguishing OVC from other cancer types, proving that REOs of serum miRNAs represent a robust and non-invasive biomarker.

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“…Moreover, we identified three miRNAs, miR-150-3p, miR-297, and miR-27b, targeting CXCL10 and CXCL8, for which there was no previous information regarding an association with DM or CKD-related diseases or a relationship with lnc-SLC15A1-1. In literature reviews, the functions of miR-150-3p and miR-297 were related to cancer [66,67]. Moreover, miR-27b-5p exerted biological effects on HUVECs, fibroblasts, and breast cancer cells in previous reports [68][69][70].…”

Section: Discussionmentioning

confidence: 98%

Indoxyl Sulfate Elevated Lnc-SLC15A1-1 Upregulating CXCL10/CXCL8 Expression in High-Glucose Endothelial Cells by Sponging MicroRNAs

Huang

Tsai

Chang

et al. 2021

Toxins

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Cardiovascular disease (CVD) is the leading cause of mortality in diabetes mellitus (DM). Immunomodulatory dysfunction is a primary feature of DM, and the emergence of chronic kidney disease (CKD) in DM abruptly increases CVD mortality compared with DM alone. Endothelial injury and the accumulation of uremic toxins in the blood of DM/CKD patients are known mechanisms for the pathogenesis of CVD. However, the molecular factors that cause this disproportional increase in CVD in the DM/CKD population are still unknown. Since long non-protein-coding RNAs (lncRNAs) play an important role in regulating multiple cellular functions, we used human endothelial cells treated with high glucose to mimic DM and with the uremic toxin indoxyl sulfate (IS) to mimic the endothelial injury associated with CKD. Differentially expressed lncRNAs in these conditions were analyzed by RNA sequencing. We discovered that lnc-SLC15A1-1 expression was significantly increased upon IS treatment in comparison with high glucose alone, and then cascaded the signal of chemokines CXCL10 and CXCL8 via sponging miR-27b, miR-297, and miR-150b. This novel pathway might be responsible for the endothelial inflammation implicated in augmenting CVD in DM/CKD and could be a therapeutic target with future clinical applications.

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FoxP3-miR-150-5p/3p suppresses ovarian tumorigenesis via an IGF1R/IRS1 pathway feedback loop

Cited by 20 publications

References 74 publications

CASC1 Expression in Bladder Cancer Is Regulated by Exosomal miRNA-150: A Comprehensive Pan-Cancer and Bioinformatics Study

CASC1 Expression in Bladder Cancer Is Regulated by Exosomal miRNA-150: A Comprehensive Pan-Cancer and Bioinformatics Study

Predict ovarian cancer by pairing serum miRNAs: Construct of single sample classifiers

Indoxyl Sulfate Elevated Lnc-SLC15A1-1 Upregulating CXCL10/CXCL8 Expression in High-Glucose Endothelial Cells by Sponging MicroRNAs

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