DDN‐AS1‐miR‐15a/16‐TCF3 feedback loop regulates tumor progression in cervical cancer

Liu, Zhihui; Wu, Meiqin; Shi, Huidong; Huang, Chong; Luo, Sukun; Song, Xiaojie

doi:10.1002/jcb.28307

Cited by 17 publications

(10 citation statements)

References 28 publications

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“…As aforementioned, TCF3 has been demonstrated correlating with poor prognosis of patients with CC in a clinical research [ 14 ]. In experimental cellular models, downregulation of TCF3 by microRNAs has been observed to suppress growth and metastasis of CC cells [ 44 , 45 ]. Therefore, silencing of TCF3 using siRNA in HeLa and SiHa cells was performed in this study, which weakened proliferation, migration, invasiveness, and resistance to death of the CC cells.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional factor 3 binds to sirtuin 1 to activate the Wnt/β-catenin signaling in cervical cancer

Bai

et al. 2022

Bioengineered

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Transcriptional factor 3 (TCF3, also termed E2A), first reported to exert crucial functions during lymphocyte development, has been revealed to participate in the pathogenesis of human cancers. The aim of this work was to investigate the function of TCF3 in cervical cancer (CC) and the molecular interactions. The bioinformatics prediction suggested that TCF3 was highly expressed in CC and linked to poor prognosis. Increased TCF3 expression was identified in CC cell lines, and its downregulation reduced proliferation and migration of CC cells in vitro as well as growth of xenograft tumors in vivo . Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that the TCF-3-related genes and genes showed differential expression between CC and normal tissues were mainly enriched in the Wnt/β-catenin pathway. TCF3 bound to sirtuin 1 (SIRT1) promoter for transcriptional activation, and SIRT1 promoted deacetylation and nuclear translocation of β-catenin in CC. SIRT1 overexpression blocked the role of TCF3 silencing and restored cell proliferation in vitro and tumor growth in vivo . Treatment with XAV-939, a β-catenin inhibitor, significantly suppressed the cell proliferation and tumor growth induced by SIRT1 overexpression. In conclusion, this study demonstrates that TCF3 augments progression of CC by activating SIRT1-mediated β-catenin signaling.

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Section: Discussionmentioning

confidence: 99%

Transcriptional factor 3 binds to sirtuin 1 to activate the Wnt/β-catenin signaling in cervical cancer

Bai

et al. 2022

Bioengineered

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“…So far, lncRNA DDN-AS1, lncRNA TMPO-AS1, lncRNA RUSC1-AS1, and Frontiers in Genetics frontiersin.org lncRNA DLEU1 have been detected to be upregulated in cervical cancer and acted as promoters in cervical carcinogenesis (Liu et al, 2018;Liu et al, 2019;Gang et al, 2020;Guo et al, 2020). LncRNA DDN-AS1-miR-15a/16-TCF3 feedback loop contributed to proliferation, migration, and invasion in cervical cancer (Liu et al, 2019). LncRNA TMPO-AS1 promoted proliferation, migration, and invasion of cervical cancer cell by regulating the miR-143-3p/ZEB1 axis (Gang et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

A novel necroptosis-related lncRNA based signature predicts prognosis and response to treatment in cervical cancer

Wang

et al. 2022

Front. Genet.

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Background: Necroptosis has been demonstrated to play a crucial role in the prognosis prediction and assessment of treatment outcome in cancers, including cervical cancer. The purpose of this study was to explore the potential prognostic value of necroptosis-related lncRNAs and their relationship with immune microenvironment and response to treatment in cervical cancer.Methods: Data from The Cancer Genome Atlas (TCGA) were collected to obtain synthetic data matrices. Necroptosis-related lncRNAs were identified by Pearson Correlation analysis. Univariate Cox and multivariate Cox regression analysis and Lasso regression were used to construct a necroptosis-related LncRNAs signature. Kaplan-Meier analysis, univariate and multivariate Cox regression analyses, receiver operating characteristic (ROC) curve, nomogram, and calibration curves analysis were performed to validate this signature. Gene set enrichment analyses (GSEA), immunoassays, and the half-maximal inhibitory concentration (IC50) were also analyzed.Results: Initially, 119 necroptosis-related lncRNAs were identified based on necroptosis-related genes and differentially expressed lncRNAs between normal and cervical cancer samples. Then, a prognostic risk signature consisting of five necroptosis-related lncRNAs (DDN-AS1, DLEU1, RGS5, RUSC1-AS1, TMPO-AS1) was established by Cox regression analysis, and LASSO regression techniques. Based on this signature, patients with cervical cancer were classified into a low- or high-risk group. Cox regression confirmed this signature as an independent prognostic predictor with an AUC value of 0.789 for predicting 1-year OS. A nomogram including signature, age, and TNM stage grade was then established, and showed an AUC of 0.82 for predicting 1-year OS. Moreover, GSEA analysis showed that immune-related pathways were enriched in the low-risk group; immunoassays showed that most immune cells, ESTIMAT scores and immune scores were negatively correlated with risk score and that the expression of immune checkpoint-proteins (CD27, CD48, CD200, and TNFRSF14) were higher in the low-risk group. In addition, patients in the low-risk group were more sensitive to Rucaparib, Navitoclax and Crizotinib than those in the high-risk group.Conclusion: We established a novel necroptosis-related lncRNA based signature to predict prognosis, tumor microenvironment and response to treatment in cervical cancer. Our study provides clues to tailor prognosis prediction and individualized immunization/targeted therapy strategies.

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“…Through the selection of prognostic lncRNAs, we identified 7 lncRNAs with significant performance in OS survival prediction, built multivariable Cox regression model under the 7 lncRNAs, and successfully stratified patients into different risk groups with distinctive survival outcomes. Notably, DDN-AS1 , one of the seven lncRNAs used by the multivariable Cox regression model, has been reported to act as competing endogenous RNA (ceRNA) that promoted the expression of TCF3 through competitively binding miR-15a and miR-16 [ 21 ], suggesting that DDN-AS1 may promote OS progression in a similar manner. We further analyzed gene expression profiles of patients in different risk groups and obtained a list of DEGs.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Characterization of Prognostic Long Noncoding RNAs in Osteosarcoma

Gao

Guo

Zhang

et al. 2020

BioMed Research International

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The molecular mechanism of osteosarcoma (OS) based on protein-coding genes has largely been studied in the past decades. However, much remains to be explored when it comes to the role that long noncoding RNAs (lncRNAs) play in the pathogenesis and progression of OS and how they are associated with OS metastasis. In the present study, we collected RNA-seq-based gene expression data of 82 OS samples from the Therapeutically Applicable Research To Generate Effective Treatments (TARGET) database, along with their clinical information. We found that 50 lncRNAs were significantly associated with patients’ survival by univariable Cox regression model. Moreover, we built multivariable Cox regression model based on 7 lncRNAs and successfully stratified patients into two risk groups, which exhibited significantly different prognostic outcomes. Significantly enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways detected by differential expression analysis on DEGs between the two groups with different prognostic outcomes were both immune-related, indicating that such GO terms and pathways are critical for OS survival. Among the seven lncRNA signatures, AC011442.1 was predicted to act as an oncogenic driver in OS by correlation analysis of copy number alteration (CNA) and lncRNA expression, and it was predicted to regulate AMPK and hedgehog signaling pathways. In summary, the identification of novel prognostic lncRNAs in OS could not only improved our understanding of the lncRNAs involved in OS tumorigenesis or progression but also assist the diagnosis and development of molecularly targeted therapies for OS, which in turn benefit patients’ survival.

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DDN‐AS1‐miR‐15a/16‐TCF3 feedback loop regulates tumor progression in cervical cancer

Cited by 17 publications

References 28 publications

Transcriptional factor 3 binds to sirtuin 1 to activate the Wnt/β-catenin signaling in cervical cancer

Transcriptional factor 3 binds to sirtuin 1 to activate the Wnt/β-catenin signaling in cervical cancer

A novel necroptosis-related lncRNA based signature predicts prognosis and response to treatment in cervical cancer

Comprehensive Characterization of Prognostic Long Noncoding RNAs in Osteosarcoma

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