scholarly journals Systematic Transcriptome Analysis of Synovial Sarcoma Reveals Novel Transcriptional And Post-Transcriptional Abnormalities

2021 ◽  
Author(s):  
Zhengwang Sun ◽  
Qiyue Xu ◽  
Quan Huang ◽  
Mengchen Yin ◽  
Hongqiang Zhang ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Synovial Sarcoma ◽  
Circular Rnas ◽  
Splicing Factors ◽  
Biological Processes ◽  
Gene Fusions ◽  
Muscle System ◽  
Transcriptomic Profile ◽  
Aggressive Cancer ◽  
Upregulated Genes

Abstract Background: Synovial sarcoma (SS) is a rare and aggressive cancer that can come from distinct soft tissue types including muscle and ligaments. The SS transcriptome is crucial for understanding the SS biology; however, the transcriptomic landscape of SS is still poorly understood. Methods: We performed deep total RNA sequencing on ten paired SS and tumor-adjacent tissues to systematically dissect the transcriptomic profile of SS in terms of gene expression, alternative splicing, gene fusion, and circular RNAs.Results: A total of 2,309 upregulated and downregulated genes were identified between SS and tumor-adjacent tissues. Those upregulated genes could lead to the upregulation of the cell cycle, ribosome, and DNA replication pathways, while the downregulated genes may result in the downregulation of a set of metabolic biological processes and signaling pathways. Moreover, 2,511 genes (including 21 splicing factors) were differentially alternative spliced, indicating that the deregulation of alternative splicing could be one important factor that contributes to the tumorigenesis. Additionally, we identified the known gene fusions of SS18-SSX1/SSX2 as well as 11 potentially novel gene fusions. Interestingly, 49 circular RNAs were differentially expressed and their parental genes could function in muscle contraction and muscle system processes. Conclusions: Collectively, our comprehensive dissection of the transcriptomic profile of SS from both transcriptional and post-transcriptional levels provides novel insights into the biology and underlying molecular mechanism of SS.

scholarly journals Transcriptomic Profiling of Synovial Sarcoma Reveals Novel Transcriptional and Post-Transcriptional Abnormalities

2021 ◽  
Author(s):  
Zhengwang Sun ◽  
Qiyue Xu ◽  
Quan Huang ◽  
Mengchen Yin ◽  
Hongqiang Zhang ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Synovial Sarcoma ◽  
Interaction Network ◽  
Underlying Mechanism ◽  
Soft Tissue Tumors ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Rare Type ◽  
Muscle System ◽  
Normal Tissues

Abstract BackgroundSynovial sarcoma (SS) is a rare type of cancer but relatively common in soft tissue tumors. The transcriptome landscape of SS is crucial for understanding the SS biology; however, the transcriptomic profile of SS is still poorly understood.MethodsHere we collected 10 paired SS and adjacent normal tissues, and then performed deeply total RNA sequencing to systematically dissect the transcriptomic changes of SS in terms of differential expression, alternative splicing, gene fusion, and circular RNAs. ResultsBy comparing SS with adjacent normal tissues, we identified 2309 upregulated and downregulated genes in SS. Those upregulated genes could lead to the upregulation of cell cycle, ribosome, and DNA replication pathways, while the downregulated genes may result in the downregulation of a set of metabolic biological processes and signaling pathways. Moreover, 2511 genes (including 21 splicing factors) were differentially alternative spliced, indicating that the deregulation of alternative splicing could be one important factor contributes to the tumorigenesis. Additionally, we not only detected the common fusion events of SS18-SSX1/SSX2 in SS, but also uncovered 11 novel gene fusions. Interestingly, 49 circular RNAs (circRNAs) were differentially expressed and their parental genes could function in muscle contraction and muscle system processes. Interaction network reconstruction and exploration revealed that these differentially expressed circRNAs may function as the miRNA sponge to regulate the expression of an abundance of differentially expressed and alternatively spliced genes. ConclusionsCollectively, our results provide novel insights into the transcriptome and underlying mechanism of SS, which could benefit the diagnosis and treatment of SS.

scholarly journals Alternative splicing and cancer: a systematic review

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Yuanjiao Zhang ◽  
Jinjun Qian ◽  
Chunyan Gu ◽  
Ye Yang
Keyword(s):  
Systematic Review ◽  
Alternative Splicing ◽  
Regulatory Proteins ◽  
Regulatory Mechanisms ◽  
Circular Rnas ◽  
Splicing Factors ◽  
Therapeutic Approaches ◽  
Invasion And Metastasis ◽  
Proliferation And Apoptosis ◽  
Splicing Isoforms

AbstractThe abnormal regulation of alternative splicing is usually accompanied by the occurrence and development of tumors, which would produce multiple different isoforms and diversify protein expression. The aim of the present study was to conduct a systematic review in order to describe the regulatory mechanisms of alternative splicing, as well as its functions in tumor cells, from proliferation and apoptosis to invasion and metastasis, and from angiogenesis to metabolism. The abnormal splicing events contributed to tumor progression as oncogenic drivers and/or bystander factors. The alterations in splicing factors detected in tumors and other mis-splicing events (i.e., long non-coding and circular RNAs) in tumorigenesis were also included. The findings of recent therapeutic approaches targeting splicing catalysis and splicing regulatory proteins to modulate pathogenically spliced events (including tumor-specific neo-antigens for cancer immunotherapy) were introduced. The emerging RNA-based strategies for the treatment of cancer with abnormally alternative splicing isoforms were also discussed. However, further studies are still required to address the association between alternative splicing and cancer in more detail.

scholarly journals Insights into how environment shapes post-mortem RNA transcription in mouse brain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Raphael Severino Bonadio ◽  
Larissa Barbosa Nunes ◽  
Patricia Natália S. Moretti ◽  
Juliana Forte Mazzeu ◽  
Stefano Cagnin ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Mouse Brain ◽  
Molecular Mechanisms ◽  
Cell Communication ◽  
Rna Degradation ◽  
The Body ◽  
Biological Processes ◽  
Post Mortem ◽  
Gene Expression Alterations ◽  
Upregulated Genes

AbstractMost biological features that occur on the body after death were already deciphered by traditional medicine. However, the molecular mechanisms triggered in the cellular microenvironment are not fully comprehended yet. Previous studies reported gene expression alterations in the post-mortem condition, but little is known about how the environment could influence RNA degradation and transcriptional regulation. In this work, we analysed the transcriptome of mouse brain after death under three concealment simulations (air exposed, buried, and submerged). Our analyses identified 2,103 genes differentially expressed in all tested groups 48 h after death. Moreover, we identified 111 commonly upregulated and 497 commonly downregulated genes in mice from the concealment simulations. The gene functions shared by the individuals from the tested environments were associated with RNA homeostasis, inflammation, developmental processes, cell communication, cell proliferation, and lipid metabolism. Regarding the altered biological processes, we identified that the macroautophagy process was enriched in the upregulated genes and lipid metabolism was enriched in the downregulated genes. On the other hand, we also described a list of biomarkers associated with the submerged and buried groups, indicating that these environments can influence the post-mortem RNA abundance in its particular way.

scholarly journals The alternative splicing of the CD45 tyrosine phosphatase is controlled by negative regulatory trans-acting splicing factors.

1992 ◽  
Vol 267 (10) ◽  
pp. 7139-7147
Author(s):  
D.M. Rothstein ◽  
H Saito ◽  
M Streuli ◽  
S.F. Schlossman ◽  
C Morimoto
Keyword(s):  
Alternative Splicing ◽  
Tyrosine Phosphatase ◽  
Splicing Factors

scholarly journals Alternative splicing acts as an independent prognosticator in ovarian carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yan Ouyang ◽  
Kaide Xia ◽  
Xue Yang ◽  
Shichao Zhang ◽  
Li Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Regression Analysis ◽  
Alternative Splicing ◽  
Ovarian Carcinoma ◽  
Cancer Patients ◽  
Cox Regression ◽  
Excision Repair ◽  
Splicing Factors ◽  
Prognostic Signature ◽  
Cox Regression Analysis

AbstractAlternative splicing (AS) events associated with oncogenic processes present anomalous perturbations in many cancers, including ovarian carcinoma. There are no reliable features to predict survival outcomes for ovarian cancer patients. In this study, comprehensive profiling of AS events was conducted by integrating AS data and clinical information of ovarian serous cystadenocarcinoma (OV). Survival-related AS events were identified by Univariate Cox regression analysis. Then, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis were used to construct the prognostic signatures within each AS type. Furthermore, we established a splicing-related network to reveal the potential regulatory mechanisms between splicing factors and candidate AS events. A total of 730 AS events were identified as survival-associated splicing events, and the final prognostic signature based on all seven types of AS events could serve as an independent prognostic indicator and had powerful efficiency in distinguishing patient outcomes. In addition, survival-related AS events might be involved in tumor-related pathways including base excision repair and pyrimidine metabolism pathways, and some splicing factors might be correlated with prognosis-related AS events, including SPEN, SF3B5, RNPC3, LUC7L3, SRSF11 and PRPF38B. Our study constructs an independent prognostic signature for predicting ovarian cancer patients’ survival outcome and contributes to elucidating the underlying mechanism of AS in tumor development.

scholarly journals Splicing Genomics Events in Cervical Cancer: Insights for Phenotypic Stratification and Biomarker Potency

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 130
Author(s):  
Flavia Zita Francies ◽  
Sheynaz Bassa ◽  
Aristotelis Chatziioannou ◽  
Andreas Martin Kaufmann ◽  
Zodwa Dlamini
Keyword(s):  
Cervical Cancer ◽  
Alternative Splicing ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Therapy Resistance ◽  
Splicing Factors ◽  
Aberrant Splicing ◽  
Molecular Alteration ◽  
Common Cancer ◽  
Potential Biomarkers

Gynaecological cancers are attributed to the second most diagnosed cancers in women after breast cancer. On a global scale, cervical cancer is the fourth most common cancer and the most common cancer in developing countries with rapidly increasing mortality rates. Human papillomavirus (HPV) infection is a major contributor to the disease. HPV infections cause prominent cellular changes including alternative splicing to drive malignant transformation. A fundamental characteristic attributed to cancer is the dysregulation of cellular transcription. Alternative splicing is regulated by several splicing factors and molecular changes in these factors lead to cancer mechanisms such as tumour development and progression and drug resistance. The serine/arginine-rich (SR) proteins and heterogeneous ribonucleoproteins (hnRNPs) have prominent roles in modulating alternative splicing. Evidence shows molecular alteration and expression levels in these splicing factors in cervical cancer. Furthermore, aberrant splicing events in cancer-related genes lead to chemo- and radioresistance. Identifying clinically relevant modifications in alternative splicing events and splicing variants, in cervical cancer, as potential biomarkers for their role in cancer progression and therapy resistance is scrutinised. This review will focus on the molecular mechanisms underlying the aberrant splicing events in cervical cancer that may serve as potential biomarkers for diagnosis, prognosis, and novel drug targets.

scholarly journals Identification of Key Candidate Genes Involved in the Progression of Idiopathic Pulmonary Fibrosis

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1123
Author(s):  
Yu Cui ◽  
Jie Ji ◽  
Jiwei Hou ◽  
Yi Tan ◽  
Xiaodong Han
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Candidate Genes ◽  
Expression Profiles ◽  
Biological Processes ◽  
Protein Protein Interaction ◽  
Novel Treatments ◽  
Kegg Pathway Analysis ◽  
Cell Components ◽  
Upregulated Genes

Idiopathic pulmonary fibrosis (IPF) is a lethal, agnogenic interstitial lung disease with limited therapeutic options. To investigate vital genes involved in the development of IPF, we integrated and compared four expression profiles (GSE110147, GSE53845, GSE24206, and GSE10667), including 87 IPF samples and 40 normal samples. By reanalyzing these datasets, we managed to identify 62 upregulated genes and 20 downregulated genes in IPF samples compared with normal samples. Differentially expressed genes (DEGs) were analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to illustrate relevant pathways of IPF, biological processes, molecular function, and cell components. The DEGs were then subjected to protein–protein interaction (PPI) for network analysis, serving to find 11 key candidate genes (ANXA3, STX11, THBS2, MMP1, MMP9, MMP7, MMP10, SPP1, COL1A1, ITGB8, IGF1). The result of RT-qPCR and immunohistochemical staining verified our finding as well. In summary, we identified 11 key candidate genes related to the process of IPF, which may contribute to novel treatments of IPF.

scholarly journals Trans-acting Factors Required for Inclusion of Regulated Exons in the Ultrabithorax mRNAs of Drosophila melanogaster

Genetics ◽  
1999 ◽  
Vol 151 (4) ◽  
pp. 1517-1529 ◽  
Author(s):  
James M Burnette ◽  
Allyson R Hatton ◽  
A Javier Lopez
Keyword(s):  
Drosophila Melanogaster ◽  
Alternative Splicing ◽  
P Element ◽  
Splicing Factors ◽  
Loss Of Function ◽  
Large Collection ◽  
Splicing Pattern ◽  
Alternatively Spliced ◽  
Hypomorphic Alleles

Abstract Alternatively spliced Ultrabithorax mRNAs differ by the presence of internal exons mI and mII. Two approaches were used to identify trans-acting factors required for inclusion of these cassette exons. First, mutations in a set of genes implicated in the control of other alternative splicing decisions were tested for dominant effects on the Ubx alternative splicing pattern. To identify additional genes involved in regulation of Ubx splicing, a large collection of deficiencies was tested first for dominant enhancement of the haploinsufficient Ubx haltere phenotype and second for effects on the splicing pattern. Inclusion of the cassette exons in Ubx mRNAs was reduced strongly in heterozygotes for hypomorphic alleles of hrp48, which encodes a member of the hnRNP A/B family and is implicated in control of P-element splicing. Significant reductions of mI and mII inclusion were also observed in heterozygotes for loss-of-function alleles of virilizer, fl(2)d, and crooked neck. The products of virilizer and fl(2)d are also required for Sxl autoregulation at the level of splicing; crooked neck encodes a protein with structural similarities to yeast-splicing factors Prp39p and Prp42p. Deletion of at least five other loci caused significant reductions in the inclusion of mI and/or mII. Possible roles of identified factors are discussed in the context of the resplicing strategy for generation of alternative Ubx mRNAs.

scholarly journals Characterization of alternative splicing events and prognostic signatures in breast cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Pihua Han ◽  
Jingjun Zhu ◽  
Guang Feng ◽  
Zizhang Wang ◽  
Yanni Ding
Keyword(s):  
Breast Cancer ◽  
Alternative Splicing ◽  
Proportional Hazards ◽  
Pearson Correlation ◽  
Original Data ◽  
Cox Proportional Hazards ◽  
Prognostic Indicators ◽  
Splicing Factors ◽  
Rna Seq

Abstract Background Breast cancer (BRCA) is one of the most common cancers worldwide. Abnormal alternative splicing (AS) frequently observed in cancers. This study aims to demonstrate AS events and signatures that might serve as prognostic indicators for BRCA. Methods Original data for all seven types of splice events were obtained from TCGA SpliceSeq database. RNA-seq and clinical data of BRCA cohorts were downloaded from TCGA database. Survival-associated AS events in BRCA were analyzed by univariate COX proportional hazards regression model. Prognostic signatures were constructed for prognosis prediction in patients with BRCA based on survival-associated AS events. Pearson correlation analysis was performed to measure the correlation between the expression of splicing factors (SFs) and the percent spliced in (PSI) values of AS events. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were conducted to demonstrate pathways in which survival-associated AS event is enriched. Results A total of 45,421 AS events in 21,232 genes were identified. Among them, 1121 AS events in 931 genes significantly correlated with survival for BRCA. The established AS prognostic signatures of seven types could accurately predict BRCA prognosis. The comprehensive AS signature could serve as independent prognostic factor for BRCA. A SF-AS regulatory network was therefore established based on the correlation between the expression levels of SFs and PSI values of AS events. Conclusions This study revealed survival-associated AS events and signatures that may help predict the survival outcomes of patients with BRCA. Additionally, the constructed SF-AS networks in BRCA can reveal the underlying regulatory mechanisms in BRCA.

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