MicroRNA-22-3p targeted regulating transcription factor 7-like 2 (TCF7L2) constrains the Wnt/β-catenin pathway and malignant behavior in osteosarcoma

Xue, YuanLiang; Guo, Ya; Liu, Ning; Deng, Zexiang; Jian, Yanping; Cai, Hongwei; Meng, Xiangqi

doi:10.1080/21655979.2021.2003942

Cited by 13 publications

(6 citation statements)

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“…The SRSF3 gene (serine and arginine rich splicing factor 3) has been reported to play a critical role in cell proliferation by promoting the G2/M transition, and preventing the death of apoptotic cells in cancers where it functions as an oncogene [ 42 ]. TCF7L2 (transcription factor 7 like 2) is a key factor in the Wnt signaling pathway, one of the 3 main cancer stem cell (CSC) pathways, and functions as an oncogene in osteosarcoma [ 43 ]. Transactivated by ERK/JNK-c-JUN/c-FOS, FOXP1 (forkhead box P1) drives osteosarcoma development by regulating the cascade of p53-P21/RB signaling [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic and predictive value of super-enhancer-derived signatures for survival and lung metastasis in osteosarcoma

Huang,

Zhang,

et al. 2024

J Transl Med

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Background Risk stratification and personalized care are crucial in managing osteosarcoma due to its complexity and heterogeneity. However, current prognostic prediction using clinical variables has limited accuracy. Thus, this study aimed to explore potential molecular biomarkers to improve prognostic assessment. Methods High-throughput inhibitor screening of 150 compounds with broad targeting properties was performed and indicated a direction towards super-enhancers (SEs). Bulk RNA-seq, scRNA-seq, and immunohistochemistry (IHC) were used to investigate SE-associated gene expression profiles in osteosarcoma cells and patient tissue specimens. Data of 212 osteosarcoma patients who received standard treatment were collected and randomized into training and validation groups for retrospective analysis. Prognostic signatures and nomograms for overall survival (OS) and lung metastasis-free survival (LMFS) were developed using Cox regression analyses. The discriminatory power, calibration, and clinical value of nomograms were evaluated. Results High-throughput inhibitor screening showed that SEs significantly contribute to the oncogenic transcriptional output in osteosarcoma. Based on this finding, focus was given to 10 SE-associated genes with distinct characteristics and potential oncogenic function. With multi-omics approaches, the hyperexpression of these genes was observed in tumor cell subclusters of patient specimens, which were consistently correlated with poor outcomes and rapid metastasis, and the majority of these identified SE-associated genes were confirmed as independent risk factors for poor outcomes. Two molecular signatures were then developed to predict survival and occurrence of lung metastasis: the SE-derived OS-signature (comprising LACTB, CEP55, SRSF3, TCF7L2, and FOXP1) and the SE-derived LMFS-signature (comprising SRSF3, TCF7L2, FOXP1, and APOLD1). Both signatures significantly improved prognostic accuracy beyond conventional clinical factors. Conclusions Oncogenic transcription driven by SEs exhibit strong associations with osteosarcoma outcomes. The SE-derived signatures developed in this study hold promise as prognostic biomarkers for predicting OS and LMFS in patients undergoing standard treatments. Integrative prognostic models that combine conventional clinical factors with these SE-derived signatures demonstrate substantially improved accuracy, and have the potential to facilitate patient counseling and individualized management.

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Section: Discussionmentioning

confidence: 99%

Prognostic and predictive value of super-enhancer-derived signatures for survival and lung metastasis in osteosarcoma

Huang,

Zhang,

et al. 2024

J Transl Med

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“…[41][42][43] It has been confirmed that miR-22-3p can inhibit osteosarcoma progression by targeting and regulating Transcription Factor 7 Like 2. [44] Low miR-125-5p expression is associated with the progression of various tumors. [45][46][47] In addition, miR-125-5p inhibits the proliferation and invasion of breast cancer cells by targeting and regulating Tumor Protein D52.…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of SKA1-related ceRNA network and SKA1 immunoassays in HCC: A study based on bioinformatic

Zeng,

Xu,

Zhuang

2023

Medicine

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Hepatocellular carcinoma (HCC) poses a global health challenge. Effective biomarkers are required for early diagnosis to improve survival rates of patients with HCC. Spindle and kinetochore-associated complex subunits 1 (SKA1) is essential for proper chromosome segregation in the mitotic cell cycle. Previous studies have shown that overexpression of SKA1 is associated with a poor prognosis in various cancers. The expression, prognostic value, and clinical functions of SKA1 in HCC were evaluated with several bioinformatics web portals. Additionally, we identified target long non-coding RNAs (lncRNAs) and microRNAs by analyzing messenger RNA (mRNA)-miRNA and miRNA-lncRNA interaction data and elucidated the potential competing endogenous RNA (ceRNA) mechanism associated with SKA1. High SKA1 expression was associated with poor prognosis in patients with HCC. Furthermore, multivariate Cox regression analysis revealed that SKA1 expression was an independent prognostic factor for HCC. GO and KEGG analyses showed that SKA1 is related to the cell cycle checkpoints, DNA replication and repair, Rho GTPases signaling, mitotic prometaphase, and kinesins. Gene set enrichment analysis revealed that high levels of SKA1 are associated with cancer-promoting pathways. DNA methylation of SKA1 in HCC tissues was lower than that in normal tissues. Ultimately, the following 9 potential ceRNA-based pathways targeting SKA1 were identified: lncRNA: AC026401.3, Small Nucleolar RNA Host Gene 3 (SNHG3), and AC124798.1-miR-139-5p-SKA1; lncRNA: AC26356.1, Small Nucleolar RNA Host Gene 16 (SNHG16), and FGD5 Antisense RNA 1-miR-22-3p-SKA1; lncRNA: Cytoskeleton Regulator RNA (CYTOR), MIR4435-2 Host Gene, and differentiation antagonizing non-protein coding RNA-miR-125b-5p-SKA1. SKA1 expression levels significantly correlated with immune cell infiltration and immune checkpoint genes in the HCC tissues. SKA1 is a potential prognostic biomarker for HCC. This study provides a meaningful direction for research on SKA1-related mechanisms, which will be beneficial for future research on HCC-related molecular biological therapies and targeted immunotherapy.

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“…The Wnt/β-Catenin signaling pathway facilitates cancer cells proliferation and differentiation, which serves a fundamental role in tumorigenesis [ 41 ]. Recent evidence shows that several microRNAs could regulate the Wnt/β-Catenin pathway, for instance, by miR-22-3p, miR-30b and miR-377-3p in OS [ 42–44 ]. Meanwhile, miR-331-3p up-regulation in pancreatic cancer cells has been shown to activate the Wnt/β-Catenin pathway [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA miR-331-3p suppresses osteosarcoma progression via the Bcl-2/Bax and Wnt/β-Catenin signaling pathways and the epithelial-mesenchymal transition by targeting N-acetylglucosaminyltransferase I (MGAT1)

Yang

Xing

et al. 2022

Bioengineered

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Osteosarcoma (OS) is a high-grade malignant disease that is a prevalent primary malignant sarcoma of the bone. The purpose of this investigation was to therefore elucidate the association between miR-331-3p and OS development and to identify a potential underlying mechanism. Key genes involved in OS were selected using GSE65071 dataset from the Gene Expression Omnibus (GEO) database and Gene Expression Profiling Interactive Analysis (GEPIA). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting were conducted to detect miR-331-3p, MGAT1, the epithelial-mesenchymal transition (EMT), Bcl-2/Bax and Wnt/β-Catenin signaling pathways related proteins. Dual-luciferase reporter assay and TargetScan were used for validating interaction between MGAT1 mRNA and miR-331-3p. Biological effects of miR-331-3p and MGAT1 on OS cells were detected employing MTT, Transwell, wound healing and flow cytometry, respectively. MiR-331-3p was under-expressed in OS, and up-regulation or inhibition of its expression could significantly inhibit or promote the malignant phenotypes of OS cells. Furthermore, we found that MGAT1, a target of miR-331-3p, had elevated expression in OS. Interestingly, MGAT1 could partially alleviate the effect of miR-331-3p in vitro . Collectively, miR-331-3p acts as an critical tumor suppressor through inhibiting MGAT1, results in suppressed Wnt/β-Catenin pathway and decreased proliferation of OS cells; leads to increased apoptosis via Bcl-2/Bax pathway and inhibited migration and invasion ability via the EMT.

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MicroRNA-22-3p targeted regulating transcription factor 7-like 2 (TCF7L2) constrains the Wnt/β-catenin pathway and malignant behavior in osteosarcoma

Cited by 13 publications

References 50 publications

Prognostic and predictive value of super-enhancer-derived signatures for survival and lung metastasis in osteosarcoma

Prognostic and predictive value of super-enhancer-derived signatures for survival and lung metastasis in osteosarcoma

Integrated analysis of SKA1-related ceRNA network and SKA1 immunoassays in HCC: A study based on bioinformatic

MicroRNA miR-331-3p suppresses osteosarcoma progression via the Bcl-2/Bax and Wnt/β-Catenin signaling pathways and the epithelial-mesenchymal transition by targeting N-acetylglucosaminyltransferase I (MGAT1)

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