scholarly journals Alternative splicing events implicated in carcinogenesis and prognosis of thyroid gland cancer

2020 ◽  
Author(s):  
zenghong wu ◽  
Yi Zhong ◽  
Fu-Cheng Cai
Keyword(s):  
Thyroid Cancer ◽  
Alternative Splicing ◽  
Practical Knowledge ◽  
Splice Variants ◽  
Expression Patterns ◽  
Prognostic Models ◽  
Clinicopathological Parameters ◽  
Oncology Research ◽  
Kaplan Meier ◽  
Alternative Splicing Events

Abstract Background: Alternative splicing events (ASEs), a critical post-transcriptional regulatory mechanism, expands gene expression patterns, resulting in increased protein diversity and more than 95% of human genes experience AS and encode splice variants in the regular physiological processes. While the role of AS in the thyroid cancer as yet missing, therefore, it was necessary to carry out this study to provide more information about the combination of splicing and clinical parameters, as well as potential mechanism of the survival-related splicing events in thyroid cancer. Materials and methods: Here, we draw all-around AS profiles of thyroid cancer by analyzing RNA-seq data. We also constructed prognostic models via combining splicing signatures and clinicopathological parameters. Splicing network was constructed as a way to offer functional insight into the full practical knowledge of AS in the initiation and development of thyroid cancer. Results: There were 10446 genes, and 45150 AS events in 506 TC patients, which indicates that ASEs are universal in TC. Moreover, 1819 AS signatures were identified to be significantly related to OS of TC patients and among the seven types of ASES, ES was the most common, followed by AP and AT. Kaplan-Meier survival curves results suggested that seven types of ASEs were related to bad prognosis in TC patients (P<0.05). In TC, AA (AUC: 0.937), AD (AUC: 0.965), AT (AUC: 0.964), ES (AUC: 0.999), ME (AUC: 0.999), RI (AUC: 0.837) all demonstrated an AUC over 0.6, of which ES and ME best predict the incidence of TC. We found that age and risk score (All) were risk factors for TC patients. As for ASEs is regulated by SFs, we study if the TC-ASEs were regulated by various SFs and the results demonstrated that the expression of 90 SFs was related to 469 ASEs OS in the TC cohort. Conclusions: In sum, the findings in the current study may provide a basis for spliceosomes in TC, and the methods used in this study could provide novel perspectives in other fields of tumor study to help shed light on future oncology research.

scholarly journals Alternative splicing events implicated in carcinogenesis and prognosis of thyroid gland cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zeng-Hong Wu ◽  
Yun Tang ◽  
Yue Zhou
Keyword(s):  
Thyroid Cancer ◽  
Alternative Splicing ◽  
Expression Patterns ◽  
Exon Skipping ◽  
Kaplan Meier ◽  
Human Genes ◽  
Transcriptional Regulatory Mechanism ◽  
Transcriptional Regulatory ◽  
Tumor Research ◽  
Alternative Splicing Events

AbstractAlternative splicing (AS), a critical post-transcriptional regulatory mechanism, expands gene expression patterns, thereby leading to increased protein diversity. Indeed, more than 95% of human genes undergo alternative splicing events (ASEs). In this study, we drew an all-around AS profile of thyroid cancer cells based on RNA-seq data. In total, there were 45,150 AS in 10,446 thyroid cancer cell genes derived from 506 patients, suggesting that ASEs is a common process in TC. Moreover, 1819 AS signatures were found to be significantly associated with the overall survival (OS) of TC patients. Kaplan–Meier survival analyses suggested that seven types of ASEs were associated with poor prognosis of TC (P < 0.05). Among them, exon skipping (ES) was the most common, with alternate promoter (AP) and alternate terminator (AT) coming second and third, respectively. Our results indicated that acceptor sites (AA) (AUC: 0.937), alternate donor sites (AD) (AUC: 0.965), AT (AUC: 0.964), ES (AUC: 0.999), mutually exclusive exons (ME) (AUC: 0.999), and retained intron (RI) (AUC: 0.837) exhibited an AUC greater than 0.6. In addition, age and risk score (All) were risk factors for TC patients. We also evaluated whether TC-ASEs are regulated by various splicing factors (SFs). We found that the expression of 90 SFs was associated with 469 ASEs and OS of TC patients. Our findings provide an insight into the role of spliceosomes in TC, which may offer novel perspectives in tumor research.

scholarly journals Systematic Profiling of Alternative Splicing Events in Ovarian Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jia Liu ◽  
Dekang Lv ◽  
Xiaobin Wang ◽  
Ruicong Wang ◽  
Xiaodong Li
Keyword(s):  
Ovarian Cancer ◽  
Alternative Splicing ◽  
Prognostic Models ◽  
Splicing Factors ◽  
Prediction Ability ◽  
Kaplan Meier ◽  
Prognosis Model ◽  
Independent Risk Factors ◽  
Prognostic Prediction ◽  
Cox Analysis

Alternative splicing (AS) is significantly related to the development of tumor and the clinical outcome of patients. In this study, our aim was to systematically analyze the survival-related AS signal in ovarian serous cystadenocarcinoma (OV) and estimate its prognostic validity in 48,049 AS events out of 21,854 genes. We studied 1,429 AS events out of 1,125 genes, which were significantly related to the overall survival (OS) in patients with OV. We established alternative splicing features on the basis of seven AS events and constructed a new comprehensive prognostic model. Kaplan-Meier curve analysis showed that seven AS characteristics and comprehensive prognostic models could strongly stratify patients with ovarian cancer and make them distinctive prognosis. ROC analysis from 0.781 to 0.888 showed that these models were highly efficient in distinguishing patient survival. We also verified the prognostic characteristics of these models in a testing cohort. In addition, uni-variate and multivariate Cox analysis showed that these models were superior independent risk factors for OS in patients with OV. Interestingly, AS events and splicing factor (SFs) networks revealed an important link between these prognostic alternative splicing genes and splicing factors. We also found that the comprehensive prognosis model signature had higher prediction ability than the mRNA signature. In summary, our study provided a possible prognostic prediction model for patients with OV and revealed the splicing network between AS and SFs, which could be used as a potential predictor and therapeutic target for patients with OV.

scholarly journals Role of global aberrant alternative splicing events in papillary thyroid cancer prognosis

Aging ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 2082-2097 ◽  
Author(s):  
Peng Lin ◽  
Rong-quan He ◽  
Zhi-guang Huang ◽  
Rui Zhang ◽  
Hua-yu Wu ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Alternative Splicing ◽  
Papillary Thyroid Cancer ◽  
Cancer Prognosis ◽  
Papillary Thyroid ◽  
Alternative Splicing Events

scholarly journals Alternative Splicing of MoPTEN Is Important for Growth and Pathogenesis in Magnaporthe oryzae

2021 ◽  
Vol 12 ◽  
Author(s):  
Shaowei Wang ◽  
Hao Liang ◽  
Yi Wei ◽  
Penghui Zhang ◽  
Yuejia Dang ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Magnaporthe Oryzae ◽  
Protein Phosphatase ◽  
Deletion Mutant ◽  
Splice Variants ◽  
Intron Retention ◽  
Expression Patterns ◽  
Plant Cells ◽  
Disease Development ◽  
Appressorium Formation

Human PTEN, a dual-phosphatase tumor suppressor, is frequently dysregulated by alternative splicing. Fungi harbor PTEN homologs, but alternative splicing of fungal PTENs has not been reported as far as we know. Here, we described an alternative splicing case in the PTEN homolog of Magnaporthe oryzae (MoPTEN). Two splice variants of MoPTEN were detected and identified, which are resulted from an intron retention and exclusion (MoPTEN-1/2). Both proteins were different in lipid and protein phosphatase activity and in expression patterns. The MoPTEN deletion mutant (ΔMoPTEN) showed the defects in conidiation, appressorium formation, and pathogenesis. ΔMoPTEN could be completely restored by MoPTEN, but rescued partially by MoPTEN-1 in the defect of conidium and appressorium formation, and by MoPTEN-2 in the defect of invasive development. Assays to assess sensitivity to oxidative stress reveal the involvement of MoPTEN-2 in scavenging exogenous and host-derived H2O2. Taken together, MoPTEN undergoes alternative splicing, and both variants cooperatively contribute to conidium and appressorium development, and invasive hyphae growth in plant cells, revealing a novel disease development pathway in M. oryzae.

scholarly journals Transcriptome analysis reveals the molecular mechanisms of heterosis on thermal resistance in hybrid abalone

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Qizhen Xiao ◽  
Zekun Huang ◽  
Yawei Shen ◽  
Yang Gan ◽  
Yi Wang ◽  
...  
Keyword(s):  
Heat Stress ◽  
Alternative Splicing ◽  
Thermal Resistance ◽  
Molecular Mechanisms ◽  
Southern China ◽  
Expression Patterns ◽  
Pathway Enrichment Analysis ◽  
High Survival ◽  
Genetic Characteristics ◽  
Alternative Splicing Events

Abstract Background Heterosis has been exploited for decades in different animals and crops due to it resulting in dramatic increases in yield and adaptability. Hybridization is a classical breeding method that can effectively improve the genetic characteristics of organisms through heterosis. Abalone has become an increasingly economically important aquaculture resource with high commercial value. However, due to changing climate, abalone is now facing serious threats of high temperature in summer. Interspecific hybrid abalone (Haliotis gigantea ♀ × H. discus hannai ♂, SD) has been cultured at large scale in southern China and has been shown high survival rates under heat stress in summer. Therefore, SD has become a good model material for heterosis research, but the molecular basis of heterosis remains elusive. Results Heterosis in thermal tolerance of SD was verified through Arrhenius break temperatures (ABT) of cardiac performance in this study. Then RNA-Sequencing was conducted to obtain gene expression patterns and alternative splicing events at control temperature (20 °C) and heat stress temperature (30 °C). A total of 356 (317 genes), 476 (435genes), and 876 (726 genes) significantly diverged alternative splicing events were identified in H. discus hannai (DD), H. gigantea (SS), and SD in response to heat stress, respectively. In the heat stress groups, 93.37% (20,512 of 21,969) of the expressed genes showed non-additive expression patterns, and over-dominance expression patterns of genes account for the highest proportion (40.15%). KEGG pathway enrichment analysis showed that the overlapping genes among common DEGs and NAGs were significantly enriched in protein processing in the endoplasmic reticulum, mitophagy, and NF-κB signaling pathway. In addition, we found that among these overlap genes, 39 genes had undergone alternative splicing events in SD. These pathways and genes may play an important role in the thermal resistance of hybrid abalone. Conclusion More alternative splicing events and non-additive expressed genes were detected in hybrid under heat stress and this may contribute to its thermal heterosis. These results might provide clues as to how hybrid abalone has a better physiological regulation ability than its parents under heat stress, to increase our understanding of heterosis in abalone.

scholarly journals Integrated bioinformatics analysis of apolipoprotein M in thyroid cancer

2019 ◽  
Author(s):  
jiang wei ◽  
Yang Yu ◽  
Jun. Zhang ◽  
Ning Xu ◽  
Guanghua Luo
Keyword(s):  
Thyroid Cancer ◽  
Regulatory Networks ◽  
Bioinformatics Analysis ◽  
Clinicopathological Parameters ◽  
Significant Prognostic Factor ◽  
Common Cancer ◽  
Kaplan Meier ◽  
Survival Gene ◽  
Cancer Tissues

Abstract Background Throid cancer is one of the most common cancer worldwide and its mechanism of development remains elusive.Apolipoprotein M (ApoM) is associated with lipid metabolism, inflammation and atherosclerosis, but the prognostic value of apoM in thyroid cancer has not been well studied.Methods In this study, transcriptional expression, survival, gene ontology and networks of apoM in patients with thyroid cancer were analyzed using integrated bioinformatics tools including UALCAN, GEO, LinkedOmics, GeneMANIA, STRING, CircNET and KOBAS.Results Results indicated that ApoM is decreased in thyroid cancer tissues and is therefore negatively associated with malignant clinicopathological parameters. However, Kaplan-Meier analyses showed that ApoM expression is not an independent and significant prognostic factor for overall survival in thyroid cancer. LinkedOmicsConclusions These results indicate that integrated bioinformatics analysis provide valuable information on apoM expression and potential regulatory networks in thyroid cancer. This information will be crucial in understanding the role of apoM in thyroid carcinogenesis.

Role of Alternative Splicing in Generating Isoform Diversity Among Plasma Membrane Calcium Pumps

2001 ◽  
Vol 81 (1) ◽  
pp. 21-50 ◽  
Author(s):  
Emanuel E. Strehler ◽  
David A. Zacharias
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Alternative Splicing ◽  
Splice Variants ◽  
Expression Patterns ◽  
Pdz Domain ◽  
Genetically Engineered ◽  
Intracellular Loop ◽  
Differential Distribution ◽  
Calcium Pumps

Calcium pumps of the plasma membrane (also known as plasma membrane Ca2+-ATPases or PMCAs) are responsible for the expulsion of Ca2+ from the cytosol of all eukaryotic cells. Together with Na+/Ca2+ exchangers, they are the major plasma membrane transport system responsible for the long-term regulation of the resting intracellular Ca2+concentration. Like the Ca2+ pumps of the sarco/endoplasmic reticulum (SERCAs), which pump Ca2+ from the cytosol into the endoplasmic reticulum, the PMCAs belong to the family of P-type primary ion transport ATPases characterized by the formation of an aspartyl phosphate intermediate during the reaction cycle. Mammalian PMCAs are encoded by four separate genes, and additional isoform variants are generated via alternative RNA splicing of the primary gene transcripts. The expression of different PMCA isoforms and splice variants is regulated in a developmental, tissue- and cell type-specific manner, suggesting that these pumps are functionally adapted to the physiological needs of particular cells and tissues. PMCAs 1 and 4 are found in virtually all tissues in the adult, whereas PMCAs 2 and 3 are primarily expressed in excitable cells of the nervous system and muscles. During mouse embryonic development, PMCA1 is ubiquitously detected from the earliest time points, and all isoforms show spatially overlapping but distinct expression patterns with dynamic temporal changes occurring during late fetal development. Alternative splicing affects two major locations in the plasma membrane Ca2+ pump protein: the first intracellular loop and the COOH-terminal tail. These two regions correspond to major regulatory domains of the pumps. In the first cytosolic loop, the affected region is embedded between a putative G protein binding sequence and the site of phospholipid sensitivity, and in the COOH-terminal tail, splicing affects pump regulation by calmodulin, phosphorylation, and differential interaction with PDZ domain-containing anchoring and signaling proteins. Recent evidence demonstrating differential distribution, dynamic regulation of expression, and major functional differences between alternative splice variants suggests that these transporters play a more dynamic role than hitherto assumed in the spatial and temporal control of Ca2+ signaling. The identification of mice carrying PMCA mutations that lead to diseases such as hearing loss and ataxia, as well as the corresponding phenotypes of genetically engineered PMCA “knockout” mice further support the concept of specific, nonredundant roles for each Ca2+ pump isoform in cellular Ca2+ regulation.

scholarly journals Alternative Splicing Generates Different Parkin Protein Isoforms: Evidences in Human, Rat, and Mouse Brain

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Soraya Scuderi ◽  
Valentina La Cognata ◽  
Filippo Drago ◽  
Sebastiano Cavallaro ◽  
Velia D'Agata
Keyword(s):  
Alternative Splicing ◽  
Parkinson Disease ◽  
Splice Variants ◽  
Expression Patterns ◽  
Gene Mutations ◽  
Protein Isoforms ◽  
Ubiquitin Protein Ligase ◽  
Gene Transcripts ◽  
Parkin Isoforms ◽  
The Brain

Parkinson protein 2, E3 ubiquitin protein ligase (PARK2) gene mutations are the most frequent causes of autosomal recessive early onset Parkinson’s disease and juvenile Parkinson disease. Parkin deficiency has also been linked to other human pathologies, for example, sporadic Parkinson disease, Alzheimer disease, autism, and cancer.PARK2primary transcript undergoes an extensive alternative splicing, which enhances transcriptomic diversification. To date severalPARK2splice variants have been identified; however, the expression and distribution of parkin isoforms have not been deeply investigated yet. Here, the currently knownPARK2gene transcripts and relative predicted encoded proteins in human, rat, and mouse are reviewed. By analyzing the literature, we highlight the existing data showing the presence of multiple parkin isoforms in the brain. Their expression emerges from conflicting results regarding the electrophoretic mobility of the protein, but it is also assumed from discrepant observations on the cellular and tissue distribution of parkin. Although the characterization of each predicted isoforms is complex, since they often diverge only for few amino acids, analysis of their expression patterns in the brain might account for the different pathogenetic effects linked toPARK2gene mutations.

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