scholarly journals Genome-wide transcriptome and translatome analyses reveal the role of protein extension and domestication in liver cancer oncogenesis

2021 ◽  
Author(s):  
Nima Wang ◽  
Dalei Wang
Keyword(s):  
Natural Selection ◽  
Liver Cancer ◽  
Stop Codon ◽  
Protein Sequences ◽  
Normal Tissues ◽  
Genome Wide ◽  
Cancer Field ◽  
Tumor Tissues ◽  
Translation Signals

ABSTRACTOne gene could be transcribed to different RNA isoforms, and then produce various forms of protein sequences. This mechanism largely diversifies the cellular pool and allows natural selection to select from a wider range of substrates. Most of the deleterious changes should be either purged or only be observed in patients with deficiencies or diseases. In the cancer field, the “intra-gene” changes between tumor and normal tissues such as the alternative splicing, stop codon read-through, or protein domestication could not be captured by differential expression analyses. In this work, we collected public transcriptome and translatome data from ten patients with liver cancer, and performed genome-wide comparison on the stop codon read-through and protein domestication events. Both events could diversify the proteome without changing the genome sequence. Surprisingly, we found that compared to normal tissues, the tumor tissues globally have significantly higher occurrence of stop codon read-through events. Similarly, the translation signals of non-coding repetitive elements (protein domestication) are elevated in tumor samples. These read-through and domestication events show limited overlapping across the ten patients, suggesting the randomness of the occurrence. It also indicates that these tumor-specific read-through and domestication events should be deleterious, and should be purged by natural selection if they are not collected timely. Our work manifests the role of protein extension and domestication in liver cancer oncogenesis, and adds new aspects to the cancer field.

scholarly journals The Intersection between Oral Microbiota, Host Gene Methylation and Patient Outcomes in Head and Neck Squamous Cell Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3425
Author(s):  
Zigui Chen ◽  
Po Yee Wong ◽  
Cherrie W. K. Ng ◽  
Linlin Lan ◽  
Sherwood Fung ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Early Detection ◽  
Patient Outcomes ◽  
Host Gene ◽  
Oral Microbiota ◽  
Gene Methylation ◽  
Normal Tissues ◽  
Oral Rinse ◽  
Tumor Tissues

The role of oral microbiota in head and neck squamous cell carcinoma (HNSCC) is poorly understood. Here we sought to evaluate the association of the bacterial microbiome with host gene methylation and patient outcomes, and to explore its potential as a biomarker for early detection or intervention. Here we performed 16S rRNA gene amplicon sequencing in sixty-eight HNSCC patients across both tissue and oral rinse samples to identify oral bacteria with differential abundance between HNSCC and controls. A subset of thirty-one pairs of HNSCC tumor tissues and the adjacent normal tissues were characterized for host gene methylation profile using bisulfite capture sequencing. We observed significant enrichments of Fusobacterium and Peptostreptococcus in HNSCC tumor tissues when compared to the adjacent normal tissues, and in HNSCC oral rinses when compared to healthy subjects, while ten other bacterial genera were largely depleted. These HNSCC-related bacteria were discriminative for HNSCC and controls with area under the receiver operating curves (AUCs) of 0.84 and 0.86 in tissue and oral rinse samples, respectively. Moreover, Fusobacterium nucleatum abundance in HNSCC cases was strongly associated with non-smokers, lower tumor stage, lower rate of recurrence, and improved disease-specific survival. An integrative analysis identified that enrichment of F. nucleatum was associated with host gene promoter methylation, including hypermethylation of tumor suppressor genes LXN and SMARCA2, for which gene expressions were downregulated in the HNSCC cohort from The Cancer Genome Atlas. In conclusion, we identified a taxonomically defined microbial consortium associated with HNSCC that may have clinical potential regarding biomarkers for early detection or intervention. Host–microbe interactions between F. nucleatum enrichment and clinical outcomes or host gene methylation imply a potential role of F. nucleatum as a pro-inflammatory driver in initiating HNSCC without traditional risk factors, which warrants further investigation for the underlying mechanisms.

scholarly journals m6A mRNA methylation regulates CTNNB1 to promote the proliferation of hepatoblastoma

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Li Liu ◽  
Jing Wang ◽  
Guifeng Sun ◽  
Qiong Wu ◽  
Ji Ma ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Stop Codon ◽  
Underlying Mechanism ◽  
Related Factors ◽  
Region Gene ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
Mrna Methylation ◽  
Rna Immunoprecipitation

Abstract Background N6-Methyladenosine (m6A) modification has been implicated in many biological processes. It is important for the regulation of messenger RNA (mRNA) stability, splicing, and translation. However, its role in cancer has not been studied in detail. Here we investigated the biological role and underlying mechanism of m6A modification in hepatoblastoma (HB). Methods We used Reverse transcription quantitative real-time PCR (RT-qPCR) and Western blotting to determine the expression of m6A related factors. And we clarified the effects of these factors on HB cells using cell proliferation assay, colony formation, apoptotic assay. Then we investigated of methyltransferase-like 13 (METTL3) and its correlation with clinicopathological features and used xenograft experiment to check METTL3 effect in vivo. m6A-Seq was used to profiled m6A transcriptome-wide in hepatoblastoma tumor tissue and normal tissue. Finally, methylated RNA immunoprecipitation (MeRIP) assay, RNA remaining assay to perform the regulator mechanism of MEETL3 on the target CTNNB1 in HB. Results In this research, we discovered that m6A modifications are increased in hepatoblastoma, and METTL3 is the main factor involved with aberrant m6A modification. We also profiled m6A across the whole transcriptome in hepatoblastoma tumor tissues and normal tissues. Our findings suggest that m6A is highly expressed in hepatoblastoma tumors. Also, m6A is enriched not only around the stop codon, but also around the coding sequence (CDS) region. Gene ontology analysis indicates that m6A mRNA methylation contributes significantly to regulate the Wnt/β-catenin pathway. Reduced m6A methylation can lead to a decrease in expression and stability of the CTNNB1. Conclusion Overall our findings suggest enhanced m6A mRNA methylation as an oncogenic mechanism in hepatoblastoma, METTL3 is significantly up-regulated in HB and promotes HB development. And identify CTNNB1 as a regulator of METTL3 guided m6A modification in HB.

scholarly journals Expression Patterns and Prognostic Values of ORMDL1 in Different Cancers

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Tengjiao Zhu ◽  
Yingtong Chen ◽  
Shuyuan Min ◽  
Fang Li ◽  
Yun Tian
Keyword(s):  
Expression Patterns ◽  
B Cell Lymphoma ◽  
Genetic Alterations ◽  
Sphingolipid Metabolism ◽  
Migration And Invasion ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
Important Regulator ◽  
Coexpressed Genes

The mammalian orosomucoid-like gene family (ORMDL), containing ORMDL1, ORMDL2, and ORMDL3, is the important regulator of sphingolipid metabolism, which is relevant to cell growth, proliferation, migration, and invasion. Since the role of ORMDL1 in cancers remained unclear, the main purpose of our study was to explore the expression patterns and prognostic values of ORMDL1 in different tumors, especially in cholangiocarcinoma (CHOL), lymphoid neoplasm diffuse large B cell lymphoma (DLBCL), acute myeloid leukemia (LAML), and thymoma (THYM). Bioinformatics tools including GEPIA, CCLE, LinkedOmics, cBioPortal, and TIMER databases were used. As a result, the expression levels of ORMDL1 in tumor tissues and normal tissues varied in different cancers, especially significantly upregulated in CHOL, DLBCL, LAML, and THYM. Moreover, ORMDL1 mRNA was also highly expressed in cell lines of DLBCL and LAML. Further studies showed that ORMDL1 overexpression was associated with poor prognosis in DLBCL, but not significant in CHOL, LAML, and THYM. Consistently, there were genetic alterations of ORMDL1 in DLBCL, and patients with genetic alterations indicated worse survival. Coexpressed genes and related biological events with ORMDL1 in DLBCL were found via LinkedOmics, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The relationship between ORMDL1 and cancer immune cells was investigated, and ORMDL1 expression was positively correlated with infiltrating levels of B cells. In conclusion, ORMDL1 is suggested to be a tumorigenic factor and considered as the potential therapeutic target and prognostic biomarker in DLBCL.

scholarly journals Genome-wide SNP genotyping highlights the role of natural selection in Plasmodium falciparumpopulation divergence

2008 ◽  
Vol 9 (12) ◽  
Author(s):  
Daniel E Neafsey ◽  
Stephen F Schaffner ◽  
Sarah K Volkman ◽  
Daniel Park ◽  
Philip Montgomery ◽  
...  
Keyword(s):  
Natural Selection ◽  
Snp Genotyping ◽  
Genome Wide

scholarly journals The role of HOMER3 in liver cancer progression.

2019 ◽  
Vol 5 (suppl) ◽  
pp. 89-89
Author(s):  
Precious Takondwa Makondi
Keyword(s):  
Liver Cancer ◽  
Viral Hepatitis ◽  
Cancer Progression ◽  
Alcohol Intake ◽  
Clinical Stage ◽  
Gene Set Enrichment Analysis ◽  
High Expression ◽  
Obesity And Diabetes ◽  
Tumor Tissues

89 Background: Liver cancer (LC) is in the seventh most common cancer and the fourth largest cause of cancer deaths. Although significant progress has been made in the prevention and treatment of viral hepatitis; alcoholic liver disease, obesity and diabetes are now emerging as major causes for LC. Recently there has been increase in identification of biomarkers which can predict LC risk and disease progression, but the roles of HOMER3 gene in LC are not known. Methods: First the expression of HOMER3 between normal and tumor tissues was determined using The Cancer Genome Atlas (TCGA), Genetic Expression Omnibus (GEO) and protein atlas datasets. HOMER3 expression at different clinical stage and overall survival (OS) was also determined. The role of HOMER3 on OS in relation to cancer stage, hepatitis virus infection and alcohol intake was also determined. STRING database determined HOMER3 interaction network and TCGA was used to verify the correlation status, and the roles of the network genes on OS. The pathways enriched by HOMER3 were determined by Gene Set Enrichment Analysis (GSEA). Results: HOMER3 was significantly highly expressed in tumor tissues as compared to normal tissues. The expression of HOMER3 correlated positively with clinical stage, with highest expression in advanced stages (Stage 3 and 4), and high HOMER3 expression was associated with poor OS. HOMER3’ s high expression was associated with poor OS in advanced stage, alcohol intake, and in those negative of viral hepatitis infection. HOMER3 interacted with HOMER1, SHANK1, GRM5, GRM1, DLGAP1, SHANK2, DLG4, SHANK3, DLG2 and DLGAP4, with positive correlation to HOMER1, SHANK1, GRM5, GRM1, DLGAP1, DLG4 and DLGAP4 and negative correlation to SHANK2, SHANK3 and DLG2. HOMER1 and DLGAP4 high expression were associated with poor OS while SHANK2, SHANK3 and DLG2 high expression were associated with favorable OS. GRM5 and GRM1 high expression were associated with favorable OS despite being positively correlated with HOMER3. ECM receptor interaction and Notch signaling were the upregulated pathways while Metabolism of xenobiotics by cytochrome p450 and PPAR signaling were the downregulated pathways. Conclusions: HOMER3 may is have a role in liver cancer progression of which its targeting may improve LC outcome.

scholarly journals Local adaptation and sexual selection drive intra-island diversification in a songbird lineage: differential divergence in autosomes and sex chromosomes

2018 ◽  
Author(s):  
Yann XC Bourgeois ◽  
Joris AM Bertrand ◽  
Boris Delahaie ◽  
Hélène Holota ◽  
Christophe Thébaud ◽  
...  
Keyword(s):  
Sexual Selection ◽  
Natural Selection ◽  
Reproductive Isolation ◽  
Local Adaptation ◽  
Sex Chromosomes ◽  
Genomic Variation ◽  
Color Variation ◽  
Mating Signals ◽  
Genome Wide

AbstractRecently diverged taxa showing marked phenotypic and ecological diversity are optimal systems to test the relative importance of two major evolutionary mechanisms, adaptation to local ecological conditions by natural selection, or mechanisms of reproductive isolation such as assortative mating mediated by sexually selected mating signals or post-zygotic incompatibilities. Whereas local adaptation is expected to affect many loci throughout the genome, traits acting as mating signals are expected to be located on sex chromosomes and have a simple genetic basis. We used genome-wide markers to test these predictions in Reunion Island’s gray-white eye (Zosterops borbonicus), which has recently diversified into five distinct plumage forms. Two of them correspond to a polymorphic highland population that is separated by a steep ecological gradient from three distinct lowland forms that show narrow contact zones in plumage color traits, yet no association with environmental variables. An analysis of population structure using genome-wide SNP loci revealed two major clades corresponding to highland and lowland forms, respectively, with the latter separated further into three independent lineages corresponding to plumage forms. Coalescent tests of alternative demographic scenarios provided support for divergence of highland and lowland lineages with an intensification of gene flow in the last 60,000 years. Landscapes of genomic variation revealed that signatures of selection associated with elevation are found at multiple regions across the genome, whereas most loci associated with the lowland forms are located on the Z sex chromosome. A gene ontology analysis identified TYRP1, a Z-linked color gene, as a likely candidate locus underlying color variation among lowland forms. Our results are consistent with the role of natural selection in driving the divergence of locally adapted highland populations, and the role of sexual selection in differentiating lowland forms through reproductive isolation mechanisms, showing that both modes of lineage divergence can take place at very small geographic scales in birds.

scholarly journals TMEM88 is a Prognostic Biomarker and Correlates With Immune Infiltrates in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Andrew Liman ◽  
Yang Gu ◽  
Pengpeng Liu ◽  
Quanyan Liu
Keyword(s):  
Liver Cancer ◽  
Cancer Progression ◽  
Prognostic Biomarker ◽  
Progression Free Survival ◽  
Free Survival ◽  
Multiple Tumor ◽  
Normal Tissues ◽  
Tumor Types ◽  
Disease Stages

Abstract BackgroundTransmembrane protein 88 (TMEM88) has emerged as a newly discovered cancer-related protein that acts as a cancer-promoting or cancer-inhibiting regulator in multiple tumor types. However, the exact role of TMEM88 in liver cancer is undetermined. The current study was designed to determine the expression of TMEM88 in liver cancer. ResultsTMEM88 expression was significantly lower in several human cancers, but higher in liver and bile cancer, than in corresponding normal tissues. TMEM88 expression in HCC tissues correlated with prognosis. Low TMEM88 expression associated with poorer overall survival, disease-specific survival, progression-free survival, and relapse-free survival in multiple cohorts of HCC patients, particularly at late disease stages (grade 2 and 3). TMEM88 showed strong correlation with tumor-infiltrating B cells, CD4+ and CD8+ T cells, macrophages, neutrophils, and dendritic cells. ConclusionThese findings demonstrate that TMEM88 is a potential prognostic biomarker that determines cancer progression and correlated with tumor immune cells infiltration in HCC.

scholarly journals Genetic Variant of NFIB is Associated With the Metastasis of Osteosarcoma in Chinese Population

2019 ◽  
Vol 18 ◽  
pp. 153303381987480 ◽  
Author(s):  
Leilei Xu ◽  
Jun Ni ◽  
Yongjie Wang ◽  
Yang Dong ◽  
Shoufeng Wang
Keyword(s):  
Messenger Rna ◽  
Chinese Population ◽  
Expression Level ◽  
Rna Expression ◽  
Single Nucleotide ◽  
Normal Tissues ◽  
Network Analyses ◽  
Genome Wide ◽  
Tumor Tissues ◽  
Genome Wide Significance

Variant rs7034162 in NFIB was reported to be associated with metastasis of osteosarcoma in European cases with genome-wide significance. Our purpose was to replicate the association of rs7034162 with the metastasis of osteosarcoma in the Chinese population and to further characterize the expression level of NFIB in osteosarcoma tissues. A total of 321 patients were included in this study. Variant rs7034162 was genotyped for each patient using the Taqman genotyping assay. Fifty-two cases of tumor tissues and adjacent normal tissues were collected during surgery. The χ2 test was used to investigate the association of rs7034162 with the metastasis of osteosarcoma. The Student t test was used to compare the gene expression between patients with metastasis and those without metastasis. The messenger RNA expression level of NFIB was then compared among different genotypes of rs7034162 with 1-way analysis of variance test. Ninety-three patients were found to have metastasis. Patients with genotype AA had remarkably higher incidence of metastasis than those with genotype TT (34.4% vs 17.1%, P = .002). Patients with metastasis were found to have significantly higher rate of allele A than those without metastasis (53.2% vs 43.9%, P = .03). The messenger RNA expression of NFIB was significantly lower in tumor tissues of patients with metastasis than in those without metastasis (0.00035 ± 0.00017 vs 0.00063 ± 0.0025, P < .001). Compared to patients with genotype TT, those with genotype AA had remarkably decreased expression of NFIB (0.00033 ± 0.0014 vs 0.00067 ± 0.00037, P = .01). Single-nucleotide polymorphism rs7034162 was associated with metastasis of osteosarcoma in the Chinese population possibly via downregulation of NFIB. Further network analyses revealing the related pathways can help elucidate the molecular mechanism of distant metastasis in patients with osteosarcoma.

scholarly journals Elevating PKM2 Expression Indicates a Biomarker of Poor Prognosis in Patients With Liver Cancer

2021 ◽  
Author(s):  
Chaoxiang Lv ◽  
Qiqi Zhang ◽  
Yuanguo Li ◽  
Entao Li ◽  
Fangxu Li ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Poor Prognosis ◽  
Cancer Metabolism ◽  
Cell Metabolism ◽  
Predictive Biomarker ◽  
Normal Tissues ◽  
Diagnosis And Prognosis ◽  
Cox Analysis ◽  
T Classification

Abstract M2 isoform of pyruvate kinase (PKM2) plays an important role in reprogramming of cell metabolism which is a hall-marker of tumorigenesis. PKM2 expression altering is closely related to cancer metabolism and tumor growth. In the present study, we analyzed the role of PKM2 expression in liver cancer in order to clarify its potential application value in the diagnosis and prognosis of liver cancer patients. In cancerous liver tissues, the PKM2 expression was significantly higher than normal tissues. High PKM2 expressing was related to patient’s age, gender, histological type, grade, stage, T classification and poor survival. Patients with Higher PKM2 expression had a shorter OS (P = 0.0013) and RFS (P = 0.027). ROC and Multivariate Cox analysis showed that high PKM2expression was a risk factor for patients’ poor prognosis. GSEA identified mitotic spindle, PI3K/Akt/mTOR signaling, notch signaling, apoptosis, G2M checkpoint and Wnt/β- Cantenin signaling were enriched with high PKM2 expression phenotype. These findings suggested PKM2 expression has potential as a predictive biomarker for the diagnosis and prognosis of patients with liver cancer.

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