scholarly journals Long Noncoding RNA RP11-357H14.17 Plays an Oncogene Role in Gastric Cancer by Activating ATF2 Signaling and Enhancing Treg Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Tang Xiaoli ◽  
Wang Wenting ◽  
Zhang Meixiang ◽  
Zuo Chunlei ◽  
Hu Chengxia

Background. Gastric cancer (GC) is one of the most common malignant tumors in the world. The potential functions and mechanisms of long noncoding RNAs (lncRNAs) in GC development are still unclear. It is of great significance to explore the prognostic value of LncRNA signatures for GC. Methods. LncRNAs differently expressed in GC and their prognostic value were studied based on The Cancer Genome Atlas (TCGA) database. The functional regulatory network and immune infiltration of RP11-357H14.17 were further studied using a variety of bioinformatics tools and databases. Results. We found that the high expression of RP11-357H14.17 was closely associated with shortened overall survival (OS) and poor prognosis in gastric cancer patients. We also found that its expression was related to clinical features including tumor volume, metastasis, and differentiation. Functional enrichment analysis revealed that RP11-357H14.17 is closely related to enhanced DNA replication and metabolism; ssGSEA analysis implied the oncogenic roles of RP11-357H14.17 was related to ATF2 signaling and Treg cell differentiation. Furthermore, we verified such link by using real-time PCR and IHC staining in human GC samples. Conclusion. We demonstrate that RP11-357H14.17 may play a crucial role in the occurrence, development, and malignant biological behavior of gastric cancer as a potential prognostic marker for gastric cancer.

2020 ◽  
Author(s):  
Lingling Gao ◽  
Xin Nie ◽  
Wenchao Zhang ◽  
Rui Gou ◽  
Yuexin Hu ◽  
...  

Abstract Background: Endometrial carcinoma (EC) is one of the most common malignant tumors in gynecology. The potential functions and mechanisms of long noncoding RNAs (lncRNAs) in the occurrence and progression of EC remains unclear. It’s meaningful to explore lncRNAs signature for providing prognostic value of EC. Methods:The differentially expressed lncRNAs and their prognostic values in EC were investigated based on The Cancer Genome Atlas (TCGA) database; the transcriptional factors (TFs), the competing endogenous RNA (ceRNA) mechanism, functional regulatory network and immune infiltration of RP11-89K21.1 and RP11-357H14.17 were further explored by various bioinformatics tools and databases. Results: We first identified high expression of RP11-89K21.1 and RP11-357H14.17 were closely associated with shorten overall survival (OS) and poor prognosis in patients with EC. We also elucidated the networks of transcription factor and co-expression genes associated with RP11-89K21.1 and RP11-357H14.17. Furthermore, the ceRNA network mechanism was successfully constructed through 2 lncRNAs (RP11-89K21.1 and RP11-357H14.17), 11 miRNAs and 183 mRNAs. Functional enrichment analysis revealed that the targeting genes of RP11-89K21.1 and RP11-357H14.17 were strongly associated with microRNAs in cancer, vessel development, growth regulation, growth factor and cell differentiation, and involved in pathways including pathways in cancer, microRNAs in cancer and apoptotic signaling pathway. Conclusions: We demonstrated for the first time that RP11-89K21.1 and RP11-357H14.17 may play crucial roles in the occurrence, development and malignant biological behavior of EC, and can be regarded as potential prognostic biomarkers for EC.


2020 ◽  
Author(s):  
Lingling Gao ◽  
Xin Nie ◽  
Wenchao Zhang ◽  
Rui Gou ◽  
Yuexin Hu ◽  
...  

Abstract Background: Endometrial carcinoma (EC) is one of the most common malignant tumors in gynecology. The potential functions and mechanisms of long noncoding RNAs (lncRNAs) in the occurrence and progression of EC remains unclear. It’s meaningful to explore lncRNAs signature for providing prognostic value of EC. Methods:The differentially expressed lncRNAs and their prognostic values in EC were investigated based on The Cancer Genome Atlas (TCGA) database; the transcriptional factors (TFs), the competing endogenous RNA (ceRNA) mechanism, functional regulatory network and immune infiltration of RP11-89K21.1 and RP11-357H14.17 were further explored by various bioinformatics tools and databases. Results: We firstly identified high expression of RP11-89K21.1 and RP11-357H14.17 were closely associated with shorten overall survival (OS) and poor prognosis in patients with EC. We also elucidated the networks of transcription factor and co-expression genes associated with RP11-89K21.1 and RP11-357H14.17. Furthermore, the ceRNA network mechanism was successfully constructed through 2 lncRNAs (RP11-89K21.1 and RP11-357H14.17), 11 miRNAs and 183 mRNAs. Functional enrichment analysis revealed that the targeting genes of RP11-89K21.1 and RP11-357H14.17 were strongly associated with microRNAs in cancer, vessel development, growth regulation, growth factor and cell differentiation, and involved in pathways including pathways in cancer, microRNAs in cancer and apoptotic signaling pathway. Conclusions: We demonstrated for the first time that RP11-89K21.1 and RP11-357H14.17 may play crucial roles in the occurrence, development and malignant biological behavior of EC, and can be regarded as potential prognostic biomarkers for EC.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qunhao Zheng ◽  
Zhiping Wang ◽  
Mengyan Zhang ◽  
Yilin Yu ◽  
Rui Chen ◽  
...  

Abstract Background Studies have shown that the Sec61 gamma subunit (SEC61G) is overexpressed in several tumors and could serve as a potential prognostic marker. However, the correlation between SEC61G and lung adenocarcinoma (LUAD) remains unclear. In the current study, we aimed to demonstrate the prognostic value and potential biological function of the SEC61G gene in LUAD. Methods Public datasets were used for SEC61G expression analyses. The prognostic value of SEC61G in LUAD was investigated using the Kaplan–Meier survival and Cox analyses. The correlation between the methylation level of SEC61G and its mRNA expression was evaluated via cBioPortal. Additionally, MethSurv was used to determine the prognostic value of the SEC61G methylation levels in LUAD. Functional enrichment analysis was conducted to explore the potential mechanism of SEC61G. Also, single sample GSEA (ssGSEA) and TIMER online tool were applied to identify the correlation between SEC61G and immune filtration. Furthermore, cell functional experiments were conducted to verify the biological behavior of SEC61G in lung adenocarcinoma cells (LAC). Results SEC61G was upregulated in pan-cancers, including LUAD. High SEC61G expression was significantly correlated with worse prognosis in LUAD patients. Multivariate analysis demonstrated that high SEC61G expression was an independent prognostic factor in the TCGA cohort. (HR = 1.760 95% CI: 1.297–2.388, p < 0.001). The methylation level of SEC61G negatively correlated with the SEC61G expression (R = − 0.290, p < 0.001), and patients with low SEC61G methylation had worse overall survival. (p = 0.0014). Proliferation-associated terms such as cell cycle and cell division were significantly enriched in GO and KEGG analysis. Vitro experiments demonstrated that knockdown of SEC61G resulted in decreased cell proliferation, invasion and facilitated apoptosis in LAC. GSEA analysis found that SEC61G expression was associated with the E2F targets. Moreover, SEC61G expression was negatively correlated with the immune cell infiltration including CD4+ T cell, CD8+ T cell, B cell, macrophage, neutrophil, and dendritic cell. Conclusion Our study indicated that overexpression of SEC61G was significantly associated with poor prognosis of LUAD patients and the malignant phenotypes of LUAD cells, suggesting that it could be a novel prognostic biomarker and potential therapeutic target of LUAD.


2020 ◽  
Author(s):  
Lingling Gao ◽  
Xin Nie ◽  
Wenchao Zhang ◽  
Rui Gou ◽  
Yuexin Hu ◽  
...  

Abstract Background: Endometrial carcinoma (EC) is one of the most common malignant tumors in gynecology. The potential functions and mechanisms of long noncoding RNAs (lncRNAs) in the occurrence and progression of EC remains unclear. It’s meaningful to explore lncRNAs signature for providing prognostic value of EC. Methods:The differentially expressed lncRNAs and their prognostic values in EC were investigated based on The Cancer Genome Atlas (TCGA) database; the transcriptional factors (TFs), the competing endogenous RNA (ceRNA) mechanism, functional regulatory network and immune infiltration of RP11-89K21.1 and RP11-357H14.17 were further explored by various bioinformatics tools and databases. Results: We first identified high expression of RP11-89K21.1 and RP11-357H14.17 were closely associated with shorten overall survival (OS) and poor prognosis in patients with EC. We also elucidated the networks of transcription factor and co-expression genes associated with RP11-89K21.1 and RP11-357H14.17. Furthermore, the ceRNA network mechanism was successfully constructed through 2 lncRNAs (RP11-89K21.1 and RP11-357H14.1), 11 miRNAs and 183 mRNAs. Functional enrichment analysis revealed that the targeting genes of RP11-89K21.1 and RP11-357H14.17 were strongly associated with microRNAs in cancer, vessel development, growth regulation, growth factor and cell differentiation, and involved in pathways including cytokine-mediated signaling pathway, transmembrane receptor protein tyrosine kinase signaling pathway and apoptotic signaling pathway. Moreover, RP11-89K21.1 and RP11-357H14.17 were correlated with immune infiltration including CD8_T cell, CD4_Tcell, Macrophage and Neutrophil. Conclusions: We demonstrated for the first time that RP11-89K21.1 and RP11-357H14.17 may play crucial roles in the occurrence, development and malignant biological behavior of EC, and can be regarded as potential prognostic biomarkers for EC.


2021 ◽  
Vol 12 ◽  
Author(s):  
Shanshan Liu ◽  
Guangchuang Yu ◽  
Li Liu ◽  
Xuejing Zou ◽  
Lang Zhou ◽  
...  

A growing amount of evidence has suggested the clinical importance of stromal and immune cells in the liver cancer microenvironment. However, reliable prognostic signatures based on assessments of stromal and immune components have not been well-established. This study aimed to identify stromal-immune score–based potential prognostic biomarkers for hepatocellular carcinoma. Stromal and immune scores were estimated from transcriptomic profiles of a liver cancer cohort from The Cancer Genome Atlas using the ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumors using Expression data) algorithm. Least absolute shrinkage and selection operator (LASSO) algorithm was applied to select prognostic genes. Favorable overall survivals and progression-free interval were found in patients with high stromal score and immune score, and 828 differentially expressed genes were identified. Functional enrichment analysis and protein–protein interaction networks further showed that these genes mainly participated in immune response, extracellular matrix, and cell adhesion. MMP9 (matrix metallopeptidase 9) was identified as a prognostic tumor microenvironment–associated gene by using LASSO and TIMER (Tumor IMmune Estimation Resource) algorithms and was found to be positively correlated with immunosuppressive molecules and drug response.


2021 ◽  
Vol 11 ◽  
Author(s):  
Haoying Wang ◽  
Xi Zeng ◽  
Ya Zheng ◽  
Yuping Wang ◽  
Yongning Zhou

Exosomes are a type of extracellular microvesicles with a diameter of 40–160 nm. Circular RNA (circRNA) is a type of closed circular RNA molecule that is highly conserved in evolution. Exosomal circRNA plays a vital role in the proliferation, invasion, migration, and drug resistance of digestive system tumors. In this study, we used The Cancer Genome Atlas (TCGA) database, UALCAN, Python crawler, miRTargetLink Human, Database for Annotation, Visualization, and Integrated Discovery (DAVID), micBioinformatic online tool, and Cytoscape software (3.7.1). The results showed that circ-RanGAP1 in gastric cancer, circUHRF1 in hepatocellular carcinoma, and circFMN2 in colorectal cancer regulate the malignant behavior of tumors and affect the expression of their host gene through sponging miR-877-3p, miR-449c-5p, and miR-1182, respectively. Twenty exosomal circRNAs regulate 6,570 target genes through sponging 23 miRNAs. Firstly, 270 of those target genes are regulated by two or more miRNAs, which are highly correlated with 83 tumor-related pathways and six Kyoto Encyclopedia of Genes and Genomes pathways. Secondly, 1,146 target genes were significantly differentially expressed in corresponding digestive system tumors, and functional enrichment analysis revealed that 78 of those were involved in 20 cancer-related pathways. In short, the bioinformatics analysis showed that these exosomal circRNAs are stably expressed in body fluids, and regulate the occurrence and development of gastric cancer, hepatocellular carcinoma, colorectal cancer, and other digestive system tumors through sponging miRNAs. Exosomal circRNAs may be used as biomarkers for the diagnosis of disease and identification of effective therapeutic targets in the future, as well as improve the prognosis of patients with digestive system tumors.


2020 ◽  
Author(s):  
Gaochen Lan ◽  
Xiaoling Yu ◽  
Yanna Zhao ◽  
Jinjian Lan ◽  
Wan Li ◽  
...  

Abstract Background: Breast cancer is the most common malignant disease among women. At present, more and more attention has been paid to long non-coding RNAs (lncRNAs) in the field of breast cancer research. We aimed to investigate the expression profiles of lncRNAs and construct a prognostic lncRNA for predicting the overall survival (OS) of breast cancer.Methods: The expression profiles of lncRNAs and clinical data with breast cancer were obtained from The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs were screened out by R package (limma). The survival probability was estimated by the Kaplan‑Meier Test. The Cox Regression Model was performed for univariate and multivariate analysis. The risk score (RS) was established on the basis of the lncRNAs’ expression level (exp) multiplied regression coefficient (β) from the multivariate cox regression analysis with the following formula: RS=exp a1 * β a1 + exp a2 * β a2 +……+ exp an * β an. Functional enrichment analysis was performed by Metascape.Results: A total of 3404 differentially expressed lncRNAs were identified. Among them, CYTOR, MIR4458HG and MAPT-AS1 were significantly associated with the survival of breast cancer. Finally, The RS could predict OS of breast cancer (RS=exp CYTOR * β CYTOR + exp MIR4458HG * β MIR4458HG + exp MAPT-AS1 * β MAPT-AS1). Moreover, it was confirmed that the three-lncRNA signature could be an independent prognostic biomarker for breast cancer (HR=3.040, P=0.000).Conclusions: This study established a three-lncRNA signature, which might be a novel prognostic biomarker for breast 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.


Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 429 ◽  
Author(s):  
Zou ◽  
Zheng ◽  
Deng ◽  
Yang ◽  
Xie ◽  
...  

Circular RNA CDR1as/ciRS-7 functions as an oncogenic regulator in various cancers. However, there has been a lack of systematic and comprehensive analysis to further elucidate its underlying role in cancer. In the current study, we firstly performed a bioinformatics analysis of CDR1as among 868 cancer samples by using RNA-seq datasets of the MiOncoCirc database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), CIBERSORT, Estimating the Proportion of Immune and Cancer cells (EPIC), and the MAlignant Tumors using Expression data (ESTIMATE) algorithm were applied to investigate the underlying functions and pathways. Functional enrichment analysis suggested that CDR1as has roles associated with angiogenesis, extracellular matrix (ECM) organization, integrin binding, and collagen binding. Moreover, pathway analysis indicated that it may regulate the TGF-β signaling pathway and ECM-receptor interaction. Therefore, we used CIBERSORT, EPIC, and the ESTIMATE algorithm to investigate the association between CDR1as expression and the tumor microenvironment. Our data strongly suggest that CDR1as may play a specific role in immune and stromal cell infiltration in tumor tissue, especially those of CD8+ T cells, activated NK cells, M2 macrophages, cancer-associated fibroblasts (CAFs) and endothelial cells. Generally, systematic and comprehensive analyses of CDR1as were conducted to shed light on its underlying pro-cancerous mechanism. CDR1as regulates the TGF-β signaling pathway and ECM-receptor interaction to serve as a mediator in alteration of the tumor microenvironment.


2019 ◽  
Vol 3 (s1) ◽  
pp. 111-111 ◽  
Author(s):  
Andrea Comba ◽  
Patrick Dunn ◽  
Anna E Argento ◽  
Padma Kadiyala ◽  
Sebastien Motsch ◽  
...  

OBJECTIVES/SPECIFIC AIMS: Oncostreams represent a novel growth pattern of GBM. In this study we uncovered the cellular and molecular mechanism that regulates the oncostreams function in GBM growth and invasion. METHODS/STUDY POPULATION: We studied oncostreams organization and function using genetically engineered mouse gliomas models (GEMM), mouse primary patient derived GBM model and human glioma biopsies. We evaluated the molecular landscape of oncostreams by laser capture microdissection (LCM) followed by RNA-Sequencing and bioinformatics analysis. RESULTS/ANTICIPATED RESULTS: Oncostreams are multicellular structures of 10-20 cells wide and 2-400 μm long. They are distributed throughout the tumors in mouse and human GBM. Oncostreams are heterogeneous structures positive for GFAP, Nestin, Olig2 and Iba1 cells and negative for Neurofilament. Using GEMM we found a negative correlation between oncostream density and animal survival. Moreover, examination of patient’s glioma biopsies evidenced that oncostreams are present in high grade but no in low grade gliomas. This suggests that oncostreams may play a role in tumor malignancy. Our data also indicated that oncostreams aid local invasion of normal brain. Transcriptome analysis of oncostreams revealed 43 differentially expressed (DE) genes. Functional enrichment analysis of DE genes showed that “collagen catabolic processes”, “positive regulation of cell migration”, and “extracellular matrix organization” were the most over-represented GO biological process. Network analysis indicated that Col1a1, ACTA2, MMP9 and MMP10 are primary target genes. These genes were also overexpressed in more malignant tumors (WT-IDH) compared to the less malignant (IDH1- R132H) tumors. Confocal time lapse imagining of 3D tumor slices demonstrated that oncostreams display a collective motion pattern within gliomas that has not been seen before. DISCUSSION/SIGNIFICANCE OF IMPACT: In summary, oncostreams are anatomically and molecularly distinctive, regulate glioma growth and invasion, display collective motion and are regulated by the extracellular matrix. We propose oncostreams as novel pathological markers valuable for diagnosis, prognosis and designing therapeutics for GBM patients.


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