scholarly journals Downregulated Expression of CLEC9A as Novel Biomarkers for Lung Adenocarcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Fang Miao ◽  
Zhiguo Lou ◽  
Shuhua Ji ◽  
Dan Wang ◽  
Yaolan Sun ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Lung Adenocarcinoma ◽  
Immune Cell ◽  
The Cancer Genome Atlas ◽  
Expression Level ◽  
Interleukin 12 ◽  
Cell Cycle Distribution ◽  
Protein Protein Interaction ◽  
Iga Production

PurposeAbnormal CLEC9A expression is concerned with carcinogenesis. However, the role of CLEC9A in lung adenocarcinoma (LUAD) remains unknown. The goal of this study was to reveal the role of CLEC9A in LUAD based on bioinformatics and cellular functional experiments.Materials and methodsData available from The Cancer Genome Atlas (TCGA) were employed to study CLEC9A expression and mutations in LUAD. Expression and alterations of CLEC9A were analyzed using UALCAN and cBioPortal, respectively. Kaplan–Meier analysis was used to analyze the effect of CLEC9A on the survival of LUAD. Protein–protein interaction (PPI) network was built using GeneMANIA analysis. The similar genes of CLEC9A were obtained using GEPIA analysis, while co-expression genes correlated with CLEC9A were identified using LinkedOmics analysis. The effects of CLEC9A expression on immune cell infiltration was assessed. The effect of CLEC9A on the proliferation, apoptosis, cell cycle distribution, and invasion of human LUAD cells was detected in the LUAD cell line.ResultsCLEC9A was downregulated and the CLEC9A gene was often altered in LUAD. The survival of LUAD patients was correlated with the expression level of CLEC9A. The similar genes of CLEC9A were linked to functional networks involving positive regulation of interleukin-12 production, plasma membrane and CD40 receptor binding, primary immunodeficiency, intestinal immune network for IgA production, and cell adhesion molecules pathways. Cell cycle, apoptosis, EMT, and RAS/MAPK were significantly enriched pathways in positive and negative correlation genes with CLEC9A. A difference in the immune infiltration level of immune cell between the high and low CLEC9A expression groups was observed. Somatic cell copy number alternations (CNAs) of the CLEC9A, including arm-level gain and arm-level deletion, observably changed the infiltration levels of B cells, CD4+ T cells, macrophages, and neutrophils in LUAD. Except for LAG3, the expression of CD274, CTLA4, PDCD1, and TIGIT was positively correlated with the expression level of CLEC9A. After transfection, overexpression and knockdown of CLEC9A could affect the proliferation, apoptosis, cell cycle distribution, and invasion of LUAD cells.ConclusionCLEC9A is associated with prognosis and tumor immune microenvironment of LUAD, suggesting that CLEC9A may be considered as a novel biomarker for LUAD.

scholarly journals ASF1B Promotes Oncogenesis in Lung Adenocarcinoma and Other Cancer Types

2021 ◽  
Vol 11 ◽  
Author(s):  
Wencheng Zhang ◽  
Zhouyong Gao ◽  
Mingxiu Guan ◽  
Ning Liu ◽  
Fanjie Meng ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Immune Cell ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Tumor Promoter ◽  
Regulatory Subunit ◽  
Cell Cycle Distribution ◽  
Cancer Type ◽  
Dependent Manner ◽  
Cancer Types

Anti-silencing function 1B histone chaperone (ASF1B) is known to be an important modulator of oncogenic processes, yet its role in lung adenocarcinoma (LUAD) remains to be defined. In this study, an integrated assessment of The Cancer Genome Atlas (TCGA) and genotype-tissue expression (GTEx) datasets revealed the overexpression of ASF1B in all analyzed cancer types other than LAML. Genetic, epigenetic, microsatellite instability (MSI), and tumor mutational burden (TMB) analysis showed that ASF1B was regulated by single or multiple factors. Kaplan-Meier survival curves suggested that elevated ASF1B expression was associated with better or worse survival in a cancer type-dependent manner. The CIBERSORT algorithm was used to evaluate immune microenvironment composition, and distinct correlations between ASF1B expression and immune cell infiltration were evident when comparing tumor and normal tissue samples. Gene set enrichment analysis (GSEA) indicated that ASF1B was associated with proliferation- and immunity-related pathways. Knocking down ASF1B impaired the proliferation, affected cell cycle distribution, and induced cell apoptosis in LUAD cell lines. In contrast, ASF1B overexpression had no impact on the malignant characteristics of LUAD cells. At the mechanistic level, ASF1B served as an indirect regulator of DNA Polymerase Epsilon 3, Accessory Subunit (POLE3), CDC28 protein kinase regulatory subunit 1(CKS1B), Dihydrofolate reductase (DHFR), as established through proteomic profiling and Immunoprecipitation-Mass Spectrometry (IP-MS) analyses. Overall, these data suggested that ASF1B serves as a tumor promoter and potential target for cancer therapy and provided us with clues to better understand the importance of ASF1B in many types of cancer.

scholarly journals GPI Is a Prognostic Biomarker and Correlates With Immune Infiltrates in Lung Adenocarcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiahui Han ◽  
Xinzhou Deng ◽  
Renhuang Sun ◽  
Ming Luo ◽  
Meng Liang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
T Cells ◽  
Lung Adenocarcinoma ◽  
Prognostic Biomarker ◽  
The Cancer Genome Atlas ◽  
Th2 Cells ◽  
Primary Therapy ◽  
Cell Proliferation Inhibition

BackgroundGlucose-6-phosphate isomerase (GPI) plays an important role in glycolysis and gluconeogenesis. However, the role of GPI in lung adenocarcinoma (LUAD) remains unclear.MethodsAll original data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and integrated via R 3.2.2. GPI expression was explored with TCGA, GEO, and Oncomine databases. Immunohistochemistry staining was used to analyze GPI expression in clinical specimens. The correlations between GPI and cancer immune characteristics were analyzed via the TIMER and TISIDB databases. GPI-specific siRNAs were used to verify the role of GPI expression on cell proliferation and cell cycle distribution.ResultsIn general, GPI is predominantly overexpressed and has reference value in the diagnosis and prognostic estimation of LUAD. Upregulated GPI was associated with poorer overall survival, clinical stage, N stage, and primary therapy outcome in LUAD. Mechanistically, we identified a hub gene that included a total of 56 GPI-related genes, which were tightly associated with the cell cycle pathway in LUAD patients. Knockdown of GPI induced cell proliferation inhibition and cell cycle arrest. GPI expression was positively correlated with infiltrating levels of Th2 cells and regulatory T cells (Tregs); in contrast, GPI expression was negatively correlated with infiltrating levels of CD8+ T cells, central memory T cells, dendritic cells, macrophages, mast cells, and eosinophils. GPI was negatively correlated with the expression of immunostimulators, such as CD40L, IL6R, and TMEM173, in LUAD.ConclusionGPI may play an important role in the cell cycle and can be used as a prognostic biomarker for determining the prognosis and immune infiltration in LUAD.

scholarly journals ARNTL2, an Immunoregulation-Related Prognostic Biomarker in Pan-Cancer and Lung Adenocarcinoma

2021 ◽  
Author(s):  
Gujie Wu ◽  
Wenmiao Wang ◽  
Zheng Yang ◽  
Qun Xue
Keyword(s):  
Lung Adenocarcinoma ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Cancer Drugs ◽  
Anti Cancer ◽  
Pan Cancer

Abstract Background ARNTL2 is a member of the PAS superfamily that promotes tumor progression. However, the role of ARNTL2 in lung adenocarcinoma (LUAD) remains unclear. The purpose of our study was to investigate the function of ARNTL2 in LUAD. Methods The expression, clinical features, and prognostic role of ARNTL2 in pan-cancer were evaluated using The Cancer Genome Atlas and Genotype-Tissue Expression data. GSEA and GSVA of ARNTL2 were performed using the R package “clusterProfiler.” The correlation between immune cell infiltration level and ARNTL2 expression was analyzed using two sources of immune cell infiltration data, including the TIMER2 and ImmuCellAI database. Finally,we analyzed the correlation between ARNTL2 and IC50 of 192 drugs. Results ARNTL2 was substantially overexpressed in LUAD and pan-cancer. High ARNTL2 expression predicted poor survival in patients with LUAD. We also found that ARNTL2 expression was positively associated with the infiltration levels of immunosuppressive cells, such as tumor associated macrophages, cancer associated fibroblasts and Tregs. Among the 192 anti-cancer drugs, ARNTL2 expression was positively correlated with IC50 of 114 anti-cancer drugs, such as SB505124, Doramapimod, Nutlin-3a (-), Sabutoclax, AZD5991, PF-4708671, Elephantin, PRIMA-1MET, Sorafenib, Vorinostat, and MK-2206. Conclusions Our results revealed that ARNTL2 is a potential prognostic biomarker in LUAD. An elevated ARNTL2 expression indicates an immunosuppressive microenvironment, and targeted therapies against ARNTL2 have excellent potential.

scholarly journals ADAMTS12 acts as a tumor microenvironment related cancer promoter in gastric cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yangming Hou ◽  
Yingjuan Xu ◽  
Dequan Wu
Keyword(s):  
Gastric Cancer ◽  
Tumor Microenvironment ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Tumor Promoter ◽  
Protein Protein Interaction ◽  
Oxidative Phosphorylation Pathway ◽  
Cox Proportional Hazard Regression

AbstractThe infiltration degree of immune and stromal cells has been shown clinically significant in tumor microenvironment (TME). However, the utility of stromal and immune components in Gastric cancer (GC) has not been investigated in detail. In the present study, ESTIMATE and CIBERSORT algorithms were applied to calculate the immune/stromal scores and the proportion of tumor-infiltrating immune cell (TIC) in GC cohort, including 415 cases from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were screened by Cox proportional hazard regression analysis and protein–protein interaction (PPI) network construction. Then ADAMTS12 was regarded as one of the most predictive factors. Further analysis showed that ADAMTS12 expression was significantly higher in tumor samples and correlated with poor prognosis. Gene Set Enrichment Analysis (GSEA) indicated that in high ADAMTS12 expression group gene sets were mainly enriched in cancer and immune-related activities. In the low ADAMTS12 expression group, the genes were enriched in the oxidative phosphorylation pathway. CIBERSORT analysis for the proportion of TICs revealed that ADAMTS12 expression was positively correlated with Macrophages M0/M1/M2 and negatively correlated with T cells follicular helper. Therefore, ADAMTS12 might be a tumor promoter and responsible for TME status and tumor energy metabolic conversion.

Deregulation of cell cycle and related microRNA expression induced by vinyl chloride monomer in hepatocytes of rats

2021 ◽  
pp. 074823372110155
Author(s):  
Weizhe Pan ◽  
Shengnan Yu ◽  
Jin Jia ◽  
Junyang Hu ◽  
Liang Jie ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Vinyl Chloride ◽  
Male Rats ◽  
Cell Cycle Distribution ◽  
Vinyl Chloride Monomer ◽  
Dynamic Changes ◽  
Cell Cycle Deregulation ◽  
Change Dynamic ◽  
Related Proteins

Vinyl chloride (VC) is a confirmed human carcinogen associated with hepatocellular carcinoma and angiosarcoma. However, the role of microRNAs (miRNAs) in liver cell cycle changes under VC exposure remains unclear, which prevents research on the mechanism of VC-induced carcinogenesis. In this study, male rats were injected intraperitoneally with VC (0, 5, 25, and 125 mg/kg body weight) for 6, 8, and 12 weeks. Cell cycle analysis of liver cells, miRNA-222, miRNA-199a, miRNA-195, and miRNA-125b expression in the liver and serum, and target protein expression were performed at different time points. The results showed a higher percentage of hepatocytes in the G1/G0 and S phases at the end of 6 and 12 weeks of VC exposure, respectively. MiRNA-222 expression decreased initially and then increased, whereas miRNA-199a, miRNA-195, and miRNA-125b expression increased initially and then decreased, which corresponded with changes in cell cycle distribution and related target proteins expression (p27, cyclinA, cyclinD1, and CDK6). The corresponding expression levels of miRNAs in serum did not change. Dynamic changes in miR-222, miR-199a, miR-195, and miR-125b induced by VC can lead to cell cycle deregulation by affecting cell cycle-related proteins, and these miRNAs can serve as early biomarkers for malignant transformation caused by VC.

scholarly journals Comprehensive Analysis of ESRRA in Endometrial Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382199208
Author(s):  
Shufang Wang ◽  
Xinlong Huo
Keyword(s):  
Endometrial Cancer ◽  
Protein Expression ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Expression Level ◽  
Operating Characteristics ◽  
Protein Expression Level ◽  
Normal Tissues

Background: Estrogen-related receptor alpha (ESRRA) was reported to play an important role in multiple biological processes of neoplastic diseases. The roles of ESRRA in endometrial cancer have not been fully investigated yet. Methods: Expression data and clinicopathological data of patients with uteri corpus endometrial carcinoma (UCEC) were obtained from The Cancer Genome Atlas (TCGA). Comprehensive bioinformatics analysis was performed, including receiver operating characteristics (ROC) curve analysis, Kaplan-Meier survival analysis, gene ontology (GO) enrichment analysis, and Gene Set Enrichment Analysis (GSEA). Immunohistochemistry was used to detect the protein expression level of ESRRA and CCK-8 assay was performed to evaluate the effect of ESRRA on the proliferation ability. Results: A total of 552 UCEC tissues and 35 normal tissues were obtained from the TCGA database. The mRNA and protein expression level of ESRRA was highly elevated in UCEC compared with normal tissues, and was closely associated with poor prognosis. ROC analysis indicated a very high diagnostic value of ESRRA for patients with UCEC. GO and GSEA functional analysis showed that ESRRA might be mainly involved in cellular metabolism processes, in turn, tumorigenesis and progression of UCEC. Knockdown of ESRRA inhibited the proliferation of UCEC cells in vitro. Further immune cell infiltration demonstrated that ESRRA enhanced the infiltration level of neutrophil cell and reduced that of T cell (CD4+ naïve), NK cell, and cancer associated fibroblast (CAF). The alteration of immune microenvironment will greatly help in developing immune checkpoint therapy for UCEC. Conclusions: Our study comprehensively analyzed the expression level, clinical value, and possible mechanisms of action of ESRRA in UCEC. These findings showed that ESRRA might be a potential diagnostic and therapeutic target.

scholarly journals Integrative and Comprehensive Pancancer Analysis of Regulator of Chromatin Condensation 1 (RCC1)

2021 ◽  
Vol 22 (14) ◽  
pp. 7374
Author(s):  
Changwu Wu ◽  
Yingjuan Duan ◽  
Siming Gong ◽  
Sonja Kallendrusch ◽  
Nikolas Schopow ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Chromatin Condensation ◽  
Treatment Strategies ◽  
Enrichment Analysis ◽  
Tissue Expression ◽  
The Cancer Genome Atlas ◽  
Malignant Neoplasms ◽  
Nucleotide Exchange ◽  
Genome Database

Regulator of Chromatin Condensation 1 (RCC1) is the only known guanine nucleotide exchange factor that acts on the Ras-like G protein Ran and plays a key role in cell cycle regulation. Although there is growing evidence to support the relationship between RCC1 and cancer, detailed pancancer analyses have not yet been performed. In this genome database study, based on The Cancer Genome Atlas, Genotype-Tissue Expression and Gene Expression Omnibus databases, the potential role of RCC1 in 33 tumors’ entities was explored. The results show that RCC1 is highly expressed in most human malignant neoplasms in contrast to healthy tissues. RCC1 expression is closely related to the prognosis of a broad variety of tumor patients. Enrichment analysis showed that some tumor-related pathways such as “cell cycle” and “RNA transport” were involved in the functional mechanism of RCC1. In particular, the conducted analysis reveals the relation of RCC1 to multiple immune checkpoint genes and suggests that the regulation of RCC1 is closely related to tumor infiltration of cancer-associated fibroblasts and CD8+ T cells. Coherent data demonstrate the association of RCC1 with the tumor mutation burden and microsatellite instability in various tumors. These findings provide new insights into the role of RCC1 in oncogenesis and tumor immunology in various tumors and indicate its potential as marker for therapy prognosis and targeted treatment strategies.

scholarly journals Identification of SHMT2 as a Potential Prognostic Biomarker and Correlating with Immune Infiltrates in Lung Adenocarcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Lianxiang Luo ◽  
Yushi Zheng ◽  
Zhiping Lin ◽  
Xiaodi Li ◽  
Xiaoling Li ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Mrna Expression ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Tumor Infiltrating Lymphocytes ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Methyl Transferase ◽  
Cox Proportional Hazard Regression

It has attracted growing attention that the role of serine hydroxy methyl transferase 2 (SHMT2) in various types of cancers. However, the prognostic role of SHMT2 in lung adenocarcinoma (LUAD) and its relationship with immune cell infiltration is not clear. In this study, the information of mRNA expression and clinic data in LUAD were, respectively, downloaded from the GEO and TCGA database. We conducted a biological analysis to select the signature gene SHMT2. Online databases including Oncomine, GEPIA, TISIDB, TIMER, and HPA were applied to analyze the characterization of SHMT2 expression, prognosis, and the correlation with immune infiltration in LUAD. The mRNA expression and protein expression of SHMT2 in LUAD tissues were higher than in normal tissue. A Kaplan-Meier analysis showed that patients with lower expression level of SHMT2 had a better overall survival rate. Multivariate analysis and the Cox proportional hazard regression model revealed that SHMT2 expression was an independent prognostic factor in patients with LUAD. Meanwhile, the gene SHMT2 was highly associated with tumor-infiltrating lymphocytes in LUAD. These results suggest that the SHMT2 gene is a promising candidate as a potential prognostic biomarker and highly associated with different types of immune cell infiltration in LUAD.

Plk3 phosphorylates topoisomerase IIα at Thr1342, a site that is not recognized by Plk1

2008 ◽  
Vol 411 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Masato Iida ◽  
Masao Matsuda ◽  
Hideya Komatani
Keyword(s):  
Cell Cycle ◽  
Kinase Assay ◽  
Cell Cycle Distribution ◽  
Physical Interaction ◽  
Topoisomerase Iiα ◽  
In Vitro Kinase Assay ◽  
A Site ◽  
Cycle Regulation

The Plk (polo-like kinase) family is involved in cell-cycle machinery. Despite the possible overlapping involvement of Plk1 and Plk3 in cell-cycle distribution, the precise role of each Plk might be different. To investigate mechanisms that may differentiate their physiological roles, we compared the substrate specificities of Plk1 and Plk3 using synthetic peptides. Among these substrate peptides, topoisomerase IIα EKT1342DDE-containing synthetic peptide was strongly phosphorylated by Plk3 but not by Plk1. By modulating the topoisomerase IIα peptide, we identified residues at positions +1, +2 and +4 as determinants of differential substrate recognition between Plk1 and Plk3. Acidic residues at positions +2 and +4 appear to be a positive determinant for Plk3 but not Plk1. Variation at position +1 appears to be tolerated by Plk3, while a hydrophobic residue at +1 is critical for Plk1 activity. The direct phosphorylation of Thr1342 of topoisomerase IIα by Plk3 was demonstrated with an in vitro kinase assay, and overexpression of Plk3 induced the phosphorylation of Thr1342 in cellular topoisomerase IIα. Furthermore, the physical interaction between Plk3 and topoisomerase IIα was also demonstrated in cells in addition to phosphorylation. These data suggest that topoisomerase IIα is a novel physiological substrate for Plk3 and that Plk1 and Plk3 play different roles in cell-cycle regulation.

CD147 Promote Proliferation in Prostate Cancer Cell

2014 ◽  
Vol 912-914 ◽  
pp. 1915-1918
Author(s):  
Qing Fang ◽  
Fang Fang ◽  
Yu Lian Liu ◽  
Wen Ping Li ◽  
Li Guo Wang
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Prostate Cancer Cell ◽  
Cell Cycle Distribution ◽  
Cell Cycle Protein ◽  
Phase Arrest ◽  
Cd147 Expression ◽  
Potential Therapeutic Application

CD147 is expressed on the cell surface of most tumor cells, which results in cancer cells proliferation, invasion, metastasis and angiogenes. Our previous study indicated that CD147 could promote invasion andmetastasis of prostate cancer. However the role of CD147 on cell proliferation has not to be explored inprostate cancer. In this study, the effects of CD147 on cell proliferation of hormone-independent prostatecancer (LNCaP-AI) was investigated. In the present study, cell cycle distribution was investigated by flowcytometry and cell cycle protein were analysis by wester blot. The results demonstrated that knock-donwn CD147 expression induced G0/G1 phase arrest, and expression of cyclin D1 has potential suppressed with western blot analysis. The results suggest that CD147 could inhibit cell prolifearion and as potential therapeutic application in treatment of proste cancer.

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