scholarly journals LINC00467 Is Upregulated by DNA Copy Number Amplification and Hypomethylation and Shows ceRNA Potential in Lung Adenocarcinoma

2022 ◽  
Vol 12 ◽  
Author(s):  
Wen Wang ◽  
Hao Bo ◽  
Yumei Liang ◽  
Guoli Li
Keyword(s):  
Lung Adenocarcinoma ◽  
Copy Number ◽  
Target Genes ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Dna Copy Number ◽  
Cerna Network ◽  
Cancer Genome Atlas ◽  
Copy Number Amplification ◽  
Genome Atlas

Lung adenocarcinoma (LUAD) is the most common histological lung cancer, and it is the leading cause of cancer-related deaths worldwide. Long noncoding RNAs (lncRNAs) have been implicated in tumorigenesis. LINC00467 is a novel lncRNA that is abnormally expressed in several cancer types including LUAD. However, its function and regulatory mechanism in LUAD progression remain unclear. In this study, based on The Cancer Genome Atlas data mining, we demonstrated that DNA copy number amplification and hypomethylation was positively correlated with LINC00467 expression in LUAD. In addition, DNA copy number amplification was significantly associated with distant metastasis, immune infiltration and poor survival. Microarray analysis demonstrated that LINC00467 knockdown in the LUAD A549 cell line led to a distinct microRNA expression profile that impacted various target genes involved in multiple biological processes. This finding suggests that LINC00467 may regulate LUAD progression by functioning as a competing endogenous RNA (ceRNA). Finally, we constructed a ceRNA network that included two microRNAs (hsa-miR-1225-5p, hsa-miR-575) and five mRNAs (BARX2, BCL9, KCNK1, KIAA1324, TMEM182) specific to LINC00467 in LUAD. Subsequent Kaplan-Meier survival analysis in both The Cancer Genome Atlas and Gene Expression Omnibus databases revealed that two genes, BARX2 and BCL9, were potential prognostic biomarkers for LUAD patients. In conclusion, our data provide possible mechanisms underlying the abnormal upregulation of LINC00467 as well as a comprehensive view of the LINC00467-mediated ceRNA network in LUAD, thereby highlighting its potential role in diagnosis and therapy.

scholarly journals Identification of Potential Signatures and Their Functions for Acute Lymphoblastic Leukemia: A Study Based on the Cancer Genome Atlas

2021 ◽  
Vol 12 ◽  
Author(s):  
Weimin Wang ◽  
Chunhui Lyu ◽  
Fei Wang ◽  
Congcong Wang ◽  
Feifei Wu ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Real Time ◽  
Lymphoblastic Leukemia ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Hub Genes ◽  
Cerna Network ◽  
Cancer Genome Atlas ◽  
Genome Atlas ◽  
Real Time Qpcr

ObjectiveAcute lymphoblastic leukemia (ALL) is a malignant disease most commonly diagnosed in adolescents and young adults. This study aimed to explore potential signatures and their functions for ALL.MethodsDifferentially expressed mRNAs (DEmRNAs) and differentially expressed long non-coding RNAs (DElncRNAs) were identified for ALL from The Cancer Genome Atlas (TCGA) and normal control from Genotype-Tissue Expression (GTEx). DElncRNA–microRNA (miRNA) and miRNA–DEmRNA pairs were predicted using online databases. Then, a competing endogenous RNA (ceRNA) network was constructed. Functional enrichment analysis of DEmRNAs in the ceRNA network was performed. Protein–protein interaction (PPI) network was then constructed. Hub genes were identified. DElncRNAs in the ceRNA network were validated using Real-time qPCR.ResultsA total of 2,903 up- and 3,228 downregulated mRNAs and 469 up- and 286 downregulated lncRNAs were identified for ALL. A ceRNA network was constructed for ALL, consisting of 845 lncRNA-miRNA and 395 miRNA–mRNA pairs. These DEmRNAs in the ceRNA network were mainly enriched in ALL-related biological processes and pathways. Ten hub genes were identified, including SMAD3, SMAD7, SMAD5, ZFYVE9, FKBP1A, FZD6, FZD7, LRP6, WNT1, and SFRP1. According to Real-time qPCR, eight lncRNAs including ATP11A-AS1, ITPK1-AS1, ANO1-AS2, CRNDE, MALAT1, CACNA1C-IT3, PWRN1, and WT1-AS were significantly upregulated in ALL bone marrow samples compared to normal samples.ConclusionOur results showed the lncRNA expression profiles and constructed ceRNA network in ALL. Furthermore, eight lncRNAs including ATP11A-AS1, ITPK1-AS1, ANO1-AS2, CRNDE, MALAT1, CACNA1C-IT3, PWRN1, and WT1-AS were identified. These results could provide a novel insight into the study of ALL.

scholarly journals METTL3-Mediated m6A mRNA Modification of FBXW7 Suppresses Lung Adenocarcinoma

2020 ◽  
Author(s):  
Yingtong Wu ◽  
Ning Chang ◽  
Yong Zhang ◽  
Xinxin Zhang ◽  
Leidi Xu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Model ◽  
Biological Effects ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Luciferase Reporter ◽  
Rna Immunoprecipitation ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Abstract BackgroundFBXW7 m6A modification plays an important role in lung adenocarcinoma (LUAD) progression; however, the underlying mechanisms remain unclear.MethodsThe correlation between FBXW7 and various genes related to m6A modification was analyzed using The Cancer Genome Atlas database. The regulatory effects of METTL3 on FBXW7 mRNA m6A modification were examined in a cell model, and the underlying mechanism was determined by methylated RNA immunoprecipitation, RNA immunoprecipitation, luciferase reporter, and mutagenesis assays. In vitro experiments were performed to further explore the biological effects of METTL3-mediated FBXW7 m6A modification on LUAD development.ResultsDecreased FBXW7 expression was accompanied by downregulated METTL3 expression in human LUAD tissues and was associated with a worse prognosis for LUAD in The Cancer Genome Atlas database. m6A was highly enriched in METTL3-mediated FBXW7 transcripts, and increased m6A modification in the coding sequence region increased its translation. Functionally, METTL3 overexpression or knockdown affected the apoptosis and proliferation phenotype of LUAD cells by regulating FBXW7 m6A modification and expression. Furthermore, FBXW7 overexpression in METTL3-depleted cells partially restored the suppression of LUAD cells in vitro and in vivo.ConclusionsOur findings reveal that METTL3 positively regulates FBXW7 expression and confirm the tumor-suppressive role of m6A-modified FBXW7, thus providing insight into its epigenetic regulatory mechanisms in LUAD initiation and development.

scholarly journals A Timely Update of Immunohistochemistry and Molecular Classification in the Diagnosis and Risk Assessment of Endometrial Carcinomas

2021 ◽  
Vol 145 (11) ◽  
pp. 1367-1378
Author(s):  
Minhua Wang ◽  
Pei Hui
Keyword(s):  
Copy Number ◽  
Treatment Strategies ◽  
The United States ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Molecular Profile ◽  
Cancer Genome Atlas ◽  
Endometrial Carcinomas ◽  
Genome Atlas

Context.— Endometrial carcinoma is the most common gynecologic malignancy in the United States and has been traditionally classified based on histology. However, the distinction of certain histologic subtypes based on morphology is not uncommonly problematic, and as such, immunohistochemical study is often needed. Advances in comprehensive tumor sequencing have provided novel molecular profiles of endometrial carcinomas. Four distinct molecular subtypes with different prognostic values have been proposed by The Cancer Genome Atlas program: polymerase epsilon ultramutated, microsatellite instability hypermutated, copy number low (microsatellite stable or no specific molecular profile), and copy number high (serouslike, p53 mutant). Objective.— To discuss the utilities of commonly used immunohistochemical markers for the classification of endometrial carcinomas and to review the recent advancements of The Cancer Genome Atlas molecular reclassification and their potential impact on treatment strategies. Data Sources.— Literature review and authors' personal practice experience. Conclusions.— The current practice of classifying endometrial cancers is predominantly based on morphology. The use of ancillary testing, including immunohistochemistry, is helpful in the identification, differential diagnosis, and classification of these cancers. New developments such as molecular subtyping have provided insightful prognostic values for endometrial carcinomas. The proposed The Cancer Genome Atlas classification is poised to gain further prominence in guiding the prognostic evaluation for tailored treatment strategies in the near future.

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