Long noncoding RNA ZNF667‐AS1 reduces tumor invasion and metastasis in cervical cancer by counteracting microRNA‐93‐3p‐dependent PEG3 downregulation

Li, Yongjie; Yang, Zhe; Wang, Yiying; Wang, Yue

doi:10.1002/1878-0261.12565

Cited by 48 publications

(37 citation statements)

References 48 publications

(44 reference statements)

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“…It is revealed that up-regulation of PEG3 protein reduced proliferation and advanced apoptosis of human glioma stem cells [20]. A study also reported that PEG3 elevation suppressed cell cycle entry and invasion in vitro as well as restrained tumor growth and metastasis in vivo in cervical cancer [31]. Furthermore, our study also showed that exosomes promoted proliferation, migration and invasion as well as inhibited apoptosis of glioma cells, enhanced the volume of tumor and Ki67 and PCNA expression as well as reduced the percentage of CD8 + T cells in glioma mice.…”

Section: Discussionmentioning

confidence: 97%

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M2 bone marrow-derived macrophage-derived exosomes shuffle microRNA-21 to accelerate immune escape of glioma by modulating PEG3

Yang

Wang

et al. 2020

Cancer Cell Int

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Background: Growing studies have focused on the role of microRNA-21 (miR-21) in glioma, thus our objective was to discuss the effect of M2 bone marrow-derived macrophage (BMDM)-derived exosomes (BMDM-Exos) shuffle miR-21 on biological functions of glioma cells by regulating paternally expressed gene 3 (PEG3). Methods: Seventy-one cases of human glioma tissues and 30 cases of non-tumor normal brain tissues were collected and stored in liquid nitrogen. PEG3 and miR-21 expression in glioma tissues was tested. The fasting venous blood of glioma patients and healthy control was collected and centrifuged, and then the supernatant was stored at − 80 °C refrigerator. The contents of interferon (IFN)-γ and transforming growth factor-β1 (TGF-β1) in serum were tested by ELISA. Glioma cells and normal glial cells were cultured to screen the target cells for further in vitro experiments. BMDM-Exos was obtained by ultra-high speed centrifugation and then was identified. BMDM-Exos was cocultured with U87 cells to detect the biological functions. The fasting venous blood of glioma patients was extracted and treated with ethylene diamine tetraacetic acid-K2 anti-freezing, and then CD8 + T cells were isolated. CD8 + T cells were co-cultured with U87 cells to detect the CD8 + T proliferation, cell cytotoxic activity, U87 cell activity, as well as IFN-γ and TGF-β1 levels. Moreover, BALB/c-nu/nu mice was taken, and the human-nude mouse glioma orthotopic transplantation model was established with U87 cells, and then mice were grouped to test the trends in tumor growth. The brain of mice (fixed by 10% formaldehyde) was sliced to detect the expression of Ki67 and proliferating cell nuclear antigen (PCNA). The spleen of mice was taken to prepare single-cell suspension, and the percentage of T lymphocytes in spleen to CD8 + T cells was detected. Results: PEG3 expression was decreased and miR-21 expression was increased in glioma cells and tissues. Depleting miR-21 or restoring PEG3 suppressed growth, migration and invasion as well as accelerated apoptosis of glioma cells, also raised CD8 + T proliferation, cell cytotoxic activity, and IFN-γ level as well as decreased U87 cell activity and TGF-β1 level. BMDM-Exos shuttle miR-21 promoted migration, proliferation and invasion as well as suppressed apoptosis of glioma cells by reducing PEG3. Exosomes enhanced the volume of tumor, Ki67 and PCNA expression, reduced the percentage of CD8 + T cells in glioma mice.

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Section: Discussionmentioning

confidence: 97%

“…Moreover, it was demonstrated that PEG3 is targeted by miR-21. According to Li et al, miR-93-3p targeted PEG3 in cervical cancer [31]. It was also presented that PEG3 is directly regulated by miR-514a-3p [32].…”

Section: Discussionmentioning

confidence: 99%

M2 bone marrow-derived macrophage-derived exosomes shuffle microRNA-21 to accelerate immune escape of glioma by modulating PEG3

Yang

Wang

et al. 2020

Cancer Cell Int

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“…ZNF667-AS1, also known as MORT, is located in 19q13.43. Dysregulated expression of ZNF667-AS1 has been reported in many tumors, including breast cancer, cervical cancer, laryngeal squamous cell carcinoma and esophageal squamous cell carcinoma [43][44][45][46]. Li et al found that ZNF667-AS1 reduces tumor invasion and metastasis in cervical cancer by counteracting microRNA-93-3p-dependent PEG3 downregulation [44].…”

Section: Discussionmentioning

confidence: 99%

“…Dysregulated expression of ZNF667-AS1 has been reported in many tumors, including breast cancer, cervical cancer, laryngeal squamous cell carcinoma and esophageal squamous cell carcinoma [43][44][45][46]. Li et al found that ZNF667-AS1 reduces tumor invasion and metastasis in cervical cancer by counteracting microRNA-93-3p-dependent PEG3 downregulation [44]. Dong et al demonstrated that aberrant hypermethylation-mediated downregulation of ZNF667-AS1 and ZNF667 correlate with progression and prognosis of esophageal squamous cell carcinoma [45].…”

Section: Discussionmentioning

confidence: 99%

Construction and Analysis of lncRNA-mediated ceRNA Network in Nasopharyngeal Carcinoma Based on Weighted Correlation Network Analysis

Zou

Huang

2020

Preprint

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Background: Increasing evidence indicated that aberrant expression of long noncoding RNAs (lncRNAs) are involved in tumorigenesis and progression of nasopharyngeal carcinoma (NPC). The purpose of this study is to construct a lncRNA-mediated ceRNA network based on Weighted correlation network analysis (WGCNA) and explore the relationship between the constituents of the ceRNA network and the prognosis of patients with NPC.Methods: In this study, WGCNA was performed on the GSE102349 to find modules of highly correlated genes. The preservation of the modules was examined by GSE68799. GSE12452 was utilized to identify the differentially expressed lncRNAs and mRNAs. GSE32960 was utilized to identify the differentially expressed miRNAs. Through annotation and intersection, the lncRNAs and mRNAs in the same WGCNA modules and the miRNAs were used to construct a ceRNA network. Next, the prognostic value of the constituents of the ceRNA network was evaluated by survival analysis. Furthermore, a risk score model for predicting progression-free survival (PFS) of NPC patients was established via lasso penalized Cox regression based on the differentially expressed genes, and the differences in the expression of the lncRNAs and mRNAs in the ceRNA network between high- and low-risk groups were investigated.Results: Fourteen stable modules were identified using GSE102349 based on WGCNA. A ceRNA network composed of 11 lncRNAs, 15 miRNAs and 40 mRNAs was established. The lncRNAs and mRNAs in this network were from turquoise and salmon modules. Survival analysis indicated that ZNF667-AS1, four mRNAs (LDHA, LMNB2, TPI1, and UNG), and hsa-miR-142-3p in the ceRNA network were significantly correlated with the prognosis of NPC. Gene set enrichment analysis indicated that the up-regulation of ZNF667-AS1 was associated with some immune-related pathways. Besides, a risk score model consisting of 12 genes was constructed and showed a good performance in predicting PFS in NPC patients. Among the 11 lncRNAs in the ceRNA network, SNHG16, SNHG17, and THAP9-AS1 were up-regulated in the high-risk group of NPC, while ZNF667-AS1 was down-regulated in the high-risk group of NPC.Conclusions: These results will promote our understanding of the crosstalk among lncRNAs, miRNAs, and mRNAs in the tumorigenesis and progression of NPC.

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“…In the existing literature, ZNF667-AS1 with low expression has been identi ed to be negatively correlated with the OS, tumor size, and FIGO stage in CC [30]. Additionally, ZNF667-AS1 can competitively bind to miR-93-3p, which targets PEG3, to regulate the progression of CC [31]. Recent research has shown that inhibiting PEG3 would promote the immune escape of cancer cells [32].…”

Section: Discussionmentioning

confidence: 99%

Immune‐related Long Noncoding RNA Signature for Patients with Cervical Cancer

Zheng

Tong

Cao

et al. 2020

Preprint

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Background: Cervical cancer (CC) is a common gynecological malignancy for which prognostic and therapeutic biomarkers are urgently needed. The signature based on immune‐related lncRNAs(IRLs) of CC has never been reported. This study aimed to establish an IRL signature for patients with CC.Methods: The RNA-seq dataset was obtained from the TCGA, GEO, and GTEx database. The immune scores（IS）based on single-sample gene set enrichment analysis (ssGSEA) were calculated to identify the IRLs, which were then analyzed using univariate Cox regression analysis to identify significant prognostic IRLs. A risk score model was established to divide patients into low-risk and high-risk groups based on the median risk score of these IRLs. This was then validated by splitting TCGA dataset(n=304) into a training-set(n=152) and a valid-set(n=152). The fraction of 22 immune cell subpopulations was evaluated in each sample to identify the differences between low-risk and high-risk groups. Additionally, a ceRNA network associated with the IRLs was constructed.Results: A cohort of 326 CC and 21 normal tissue samples with corresponding clinical information was included in this study. Twenty-eight IRLs were collected according to the Pearson’s correlation analysis between immune score and lncRNA expression (P < 0.01). Four IRLs (BZRAP1-AS1, EMX2OS, ZNF667-AS1, and CTC-429P9.1) with the most significant prognostic values (P < 0.05) were identified which demonstrated an ability to stratify patients into low-risk and high-risk groups by developing a risk score model. It was observed that patients in the low‐risk group showed longer overall survival (OS) than those in the high‐risk group in the training-set, valid-set, and total-set. The area under the curve (AUC) of the receiver operating characteristic curve (ROC curve) for the four IRLs signature in predicting the one-, two-, and three-year survival rates were larger than 0.65. In addition, the low-risk and high-risk groups displayed different immune statuses in GSEA. These IRLs were also significantly correlated with immune cell infiltration. Conclusions: Our results showed that the IRL signature had a prognostic value for CC. Meanwhile, the specific mechanisms of the four-IRLs in the development of CC were ascertained preliminarily.

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Long noncoding RNA ZNF667‐AS1 reduces tumor invasion and metastasis in cervical cancer by counteracting microRNA‐93‐3p‐dependent PEG3 downregulation

Cited by 48 publications

References 48 publications

M2 bone marrow-derived macrophage-derived exosomes shuffle microRNA-21 to accelerate immune escape of glioma by modulating PEG3

M2 bone marrow-derived macrophage-derived exosomes shuffle microRNA-21 to accelerate immune escape of glioma by modulating PEG3

Construction and Analysis of lncRNA-mediated ceRNA Network in Nasopharyngeal Carcinoma Based on Weighted Correlation Network Analysis

Immune‐related Long Noncoding RNA Signature for Patients with Cervical Cancer

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