scholarly journals An epithelial–mesenchymal transition-related long noncoding RNA signature correlates with the prognosis and progression in patients with bladder cancer

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Hang Tong ◽  
Tinghao Li ◽  
Shun Gao ◽  
Hubin Yin ◽  
Honghao Cao ◽  
...  

Abstract Bladder cancer is a common malignant tumour worldwide. Epithelial–mesenchymal transition (EMT)-related biomarkers can be used for early diagnosis and prognosis of cancer patients. To explore, accurate prediction models are essential to the diagnosis and treatment for bladder cancer. In the present study, an EMT-related long noncoding RNA (lncRNA) model was developed to predict the prognosis of patients with bladder cancer. Firstly, the EMT-related lncRNAs were identified by Pearson correlation analysis, and a prognostic EMT-related lncRNA signature was constructed through univariate and multivariate Cox regression analyses. Then, the diagnostic efficacy and the clinically predictive capacity of the signature were assessed. Finally, Gene set enrichment analysis (GSEA) and functional enrichment analysis were carried out with bioinformatics. An EMT-related lncRNA signature consisting of TTC28-AS1, LINC02446, AL662844.4, AC105942.1, AL049840.3, SNHG26, USP30-AS1, PSMB8-AS1, AL031775.1, AC073534.1, U62317.2, C5orf56, AJ271736.1, and AL139385.1 was constructed. The diagnostic efficacy of the signature was evaluated by the time-dependent receiver-operating characteristic (ROC) curves, in which all the values of the area under the ROC (AUC) were more than 0.73. A nomogram established by integrating clinical variables and the risk score confirmed that the signature had a good clinically predict capacity. GSEA analysis revealed that some cancer-related and EMT-related pathways were enriched in high-risk groups, while immune-related pathways were enriched in low-risk groups. Functional enrichment analysis showed that EMT was associated with abundant GO terms or signaling pathways. In short, our research showed that the 14 EMT-related lncRNA signature may predict the prognosis and progression of patients with bladder cancer.

2018 ◽  
Vol 12 (S4) ◽  
Author(s):  
Kuo-Sheng Hung ◽  
Chung-Chi Hsiao ◽  
Tun-Wen Pai ◽  
Chin-Hwa Hu ◽  
Wen-Shyong Tzou ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
XinJie Yang ◽  
Sha Niu ◽  
JiaQiang Liu ◽  
Jincheng Fang ◽  
ZeYu Wu ◽  
...  

AbstractGlioblastoma (GBM) is a strikingly heterogeneous and lethal brain tumor with very poor prognosis. LncRNAs play critical roles in the tumorigenesis of GBM through regulation of various cancer-related genes and signaling pathways. Here, we focused on the essential role of EMT and identified 78 upregulated EMT-related genes in GBM through differential expression analysis and Gene set enrichment analysis (GSEA). A total of 301 EMT-related lncRNAs were confirmed in GBM through Spearman correlation analysis and a prognostic signature consisting of seven EMT-related lncRNAs (AC012615.1, H19, LINC00609, LINC00634, POM121L9P, SNHG11, and USP32P3) was established by univariate and multivariate Cox regression analyses. Significantly, Kaplan–Meier analysis and receiver-operating-characteristic (ROC) curve validated the accuracy and efficiency of the signature to be satisfactory. Quantitative real-time (qRT)-PCR assay demonstrated the expression alterations of the seven lncRNAs between normal glial and glioma cell lines. Functional enrichment analysis revealed multiple EMT and metastasis-related pathways were associated with the EMT-related lncRNA prognostic signature. In addition, we observed the degree of immune cell infiltration and immune responses were significantly increased in high-risk subgroup compared with low-risk subgroup. In conclusion, we established an effective and robust EMT-related lncRNA signature which was expected to predict the prognosis and immunotherapy response for GBM patients.


2020 ◽  
pp. 1-11
Author(s):  
Daqing Shen ◽  
Jing Xu ◽  
Xiande Cao ◽  
Xianxiang Cao ◽  
Hailin Tan ◽  
...  

BACKGROUND: Long noncoding RNA (lncRNA) are critical regulators of tumor progression. OBJECTIVE: To determine how the lncRNA membrane associated guanylate kinase, WW and PDZ domain-containing 2 (MAG12) antisense RNA 3 (MAGI2-AS3) and the phosphatase and tensin homolog (PTEN) gene function in regulating bladder cancer (Bca) progression. METHODS: Total RNA from 80 and 30 paired resected Bca and para-cancerous tissues from patients with confirmed Bca was sequentially extracted, quantified, purified, and reverse transcribed using RT-PCR. A library was constructed and sequenced. Four Bca cell lines and a normal urothelial cell line were transfected with lentiviral plasmids, and cell migration and invasion were assayed in vitro. An orthotopic mouse model of Bca was created for in vivo studies. RESULTS: MAGI2-AS3 expression was significantly downregulated in Bca, compared with normal tissues, and negatively associated with tumor stage and a poor prognosis. MAGI2-AS3 and its sense RNA MAGI2 showed significant and positive correlation. The expression of MAGI2 and its downstream gene, PTEN, increased in Bca cells overexpressing MAGI2-AS3, and interference by MAGI2 expression reversed the migration and invasion inhibited by MAGI2-AS3 overexpression. CONCLUSION: MAGI2-AS3 overexpression inhibited Bca cell progression by regulating the MAGI2/PTEN/epithelial-mesenchymal transition, offering novel insights into the mechanism of Bca progression.


2021 ◽  
Vol 11 ◽  
Author(s):  
Ningning Zhao ◽  
Jiajie Zhang ◽  
Lili Zhao ◽  
Xiaoni Fu ◽  
Qian Zhao ◽  
...  

Glioblastoma multiforme (GBM) is the most common brain malignancy and major cause of high mortality in patients with GBM, and its high recurrence rate is its most prominent feature. However, the pathobiological mechanisms involved in recurrent GBM remain largely unknown. Here, whole-transcriptome sequencing (RNA-sequencing, RNA-Seq) was used in characterizing the expression profile of recurrent GBM, and the aim was to identify crucial biomarkers that contribute to GBM relapse. Differentially expressed RNAs in three recurrent GBM tissues compared with three primary GBM tissues were identified through RNA-Seq. The function and mechanism of a candidate long noncoding RNA (lncRNA) in the progression and recurrence of GBM were elucidated by performing comprehensive bioinformatics analyses, such as functional enrichment analysis, protein–protein interaction prediction, and lncRNA–miRNA–mRNA regulatory network construction, and a series of in vitro assays. As the most significantly upregulated gene identified in recurrent GBM, HSPA1A is mainly related to antigen presentation and the MAPK signaling pathway, as indicated by functional enrichment analysis. HSPA1A was predicted as the target gene of the lncRNA NONHSAT079852.2. qRT-PCR revealed that NONHSAT079852.2 was significantly elevated in recurrent GBM relative to that in primary GBM, and high NONHSAT079852.2 expression was associated with the poor overall survival rates of patients with GBM. The knockdown of NONHSAT079852.2 successfully induced tumor cell apoptosis, inhibited the proliferation, migration, invasion and the expression level of HSPA1A in glioma cells. NONHSAT079852.2 was identified to be a sponge for hsa-miR-10401-3p through luciferase reporter assay. Moreover, HSPA1A was targeted and regulated by hsa-miR-10401-3p. Collectively, the results suggested that NONHSAT079852.2 acts as a sponge of hsa-mir-10401-3p and thereby enhances HSPA1A expression, promotes tumor cell proliferation and invasion, and leads to the progression and recurrence of GBM. This study will provide new insight into the regulatory mechanisms of NONHSAT079852.2-mediated competing endogenous RNA in the pathogenesis of recurrent GBM and evidence of the potential of lncRNAs as diagnostic biomarkers or potential therapeutic targets.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yalu Zhang ◽  
Qiaofei Liu ◽  
Jingkai Liu ◽  
Quan Liao

Abstract Background CD58 has been demonstrated to be abnormally expressed in multiple hematopoietic malignancies and solid tumors and plays an essential role in tumorigenesis and progression; however, its clinical significance and prognostic value in pancreatic ductal adenocarcinoma (PDAC) remain unknown. Methods Based on diverse online public databases and 81 PDAC samples of tissue microarray-based immunohistochemistry (IHC), we evaluated CD58 expression in PDAC patients and analyzed its association with clinicopathological characteristics, clinical outcomes, and infiltration of immune cells in PDAC. Furthermore, the correlation between CD58 and the cancer stem cell (CSC)-related, epithelial–mesenchymal transition (EMT)-related, and immune-related markers were detected. Besides, the functional enrichment analysis and related pathways were analyzed and visualized. Results CD58 expression was elevated in pancreatitis and PDAC tissues than normal pancreas or adjacent nontumor tissues. The positive cases of CD58 (e.g. more than 50% positive cells) in PDAC account for 95.06% (77/81). Upregulated CD58 in cancer tissues was associated with worse histological grade, larger tumor size, and poorer overall survival and disease-free survival in PDAC patients. Furthermore, Cox multivariate regression analysis revealed that CD58 was an independent prognostic factor in PDAC. CD58 expression was correlated with infiltrations of neutrophils, CD8+ T cells, and dendritic cells (DCs). In addition, correlation gene analysis indicated that CD58 expression was strongly correlated with immune-related, EMT-related, and CSC-related markers. Functional enrichment analysis and KEGG pathway manifested that CD58 might be involved in PDAC initiation and progression. Conclusions CD58 expression is upregulated in PDAC tissues and its high expression is notably related to poor survival of PDAC. Therefore, CD58 may serve as a novel and effective marker for predicting the prognosis of PDAC patients.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yuntao Shi ◽  
Yingying Zhuang ◽  
Jialing Zhang ◽  
Mengxue Chen ◽  
Shangnong Wu

Objective. Although noncoding RNAs, especially the microRNAs, have been found to play key roles in CRC development in intestinal tissue, the specific mechanism of these microRNAs has not been fully understood. Methods. GEO and TCGA database were used to explore the microRNA expression profiles of normal mucosa, adenoma, and carcinoma. And the differential expression genes were selected. Computationally, we built the SVM model and multivariable Cox regression model to evaluate the performance of tumorigenic microRNAs in discriminating the adenomas from normal tissues and risk prediction. Results. In this study, we identified 20 miRNA biomarkers dysregulated in the colon adenomas. The functional enrichment analysis showed that MAPK activity and MAPK cascade were highly enriched by these tumorigenic microRNAs. We also investigated the target genes of the tumorigenic microRNAs. Eleven genes, including PIGF, TPI1, KLF4, RARS, PCBP2, EIF5A, HK2, RAVER2, HMGN1, MAPK6, and NDUFA2, were identified to be frequently targeted by the tumorigenic microRNAs. The high AUC value and distinct overall survival rates between the two risk groups suggested that these tumorigenic microRNAs had the potential of diagnostic and prognostic value in CRC. Conclusions. The present study revealed possible mechanisms and pathways that may contribute to tumorigenesis of CRC, which could not only be used as CRC early detection biomarkers, but also be useful for tumorigenesis mechanism studies.


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