Genetic variation of circHIBADH enhances prostate cancer risk through regulating HNRNPA1-related RNA splicing

The current study aimed to investigate associations of circRNAs and related genetic variants with the risk of prostate cancer(PCa)as well as to elucidate biological mechanisms underlying the associations.We first compared expression levels of circRNAs between 25 paired PCa and adjacent normal tissues to identify riskassociated circRNAs by using the MiOncoCirc database.We then used logistic regression models to evaluate associations between genetic variants in candidate circRNAs and PCa risk among 4662 prostate cancer patients and 3114 healthy controls,and identified circHIBADH rs11973492 T>C as a significant risk-associated variant(odds ratio=1.20,95%confidence interval:1.08-1.34,P=7.06×10^(-4))in a dominant genetic model,which altered the secondary structure of the corresponding RNA chain.In the in silico analysis,we found that circHIBADH sponged and silenced 21 RNA-binding proteins(RBPs)enriched in the RNA splicing pathway,among which HNRNPA1 was identified and validated as a hub RBP using an external RNA-sequencing data as well as the in-house(four tissue samples)and publicly available single-cell transcriptomes.Additionally,we demonstrated that HNRNPA1 influenced hallmarks including MYC target,DNA repair,and E2F target signaling pathways,thereby promoting carcinogenesis.In conclusion,genetic variants in circHIBADH may act as sponges and inhibitors of RNA splicing-associated RBPs including HNRNPA1,playing an oncogenic role in PCa.

Molecular targets and mechanisms of different aberrant alternative splicing in metastatic liver cancer

Metastasis remains a major challenge in the successful management of malignant diseases.The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon,stomach,and pancreatic cancers,as well as melanoma,breast cancer,and sarcoma.As an important factor that influences the development of metastatic liver cancer,alternative splicing drives the diversity of RNA transcripts and protein subtypes,which may provide potential to broaden the target space.In particular,the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence,progression,aggressiveness,and drug resistance of cancers caused by the selective splicing of specific genes.This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer.It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes,abnormal splicing,and the contribution of hypoxia to these changes during metastasis.

Two splicing variants of amino acid transporter-like 4(OsATL4)negatively regulate rice tillering and yield by mediating the transport of amino acids

Amino acids are the primary form of nitrogen utilization in higher plants,mainly transported by amino acid transporters.In this study,we analyzed the natural variation of amino acid transporter-like 4(OsATL4)in rice germplasm resources,identified its spatiotemporal expression characteristics,determined its substrate transport,and validated its function using transgenic plants.We found that the promoter sequence of OsATL4 varied across 498 rice varieties.The expression level of OsATL4 was higher in japonica rice,which was negatively correlated with tiller number and grain yield.OsATL4 was highly expressed in the basal part,leaf sheath,stem,and young panicle,with its two splicing variants localized to the cell membrane.OsATL4a(the long splicing variant)had a high affinity for transporting Ser,Leu,Phe,and Thr,while OsATL4b(the short splicing variant)had a high affinity for transporting Ser,Leu,and Phe.Blocking OsATL4 promoted axillary bud outgrowth,rice tillering,and grain yield,whereas overexpression lines exhibited the opposite phenotype.Exogenous application of low concentrations of Ser promoted axillary bud outgrowth in overexpression lines,while high concentrations of Ser inhibited it.Conversely,the mutant lines showed the opposite response.Altered expression of OsATL4 might affect the expression of genes in nitrogen,auxin,and cytokinin pathways.We propose that two splicing variants of OsATL4 negatively regulate rice tillering and yield by mediating the transport of amino acids,making it a significant target for high-yield rice breeding.

Alternative splicing of the PECTINESTERASE gene encoding a cell wall-degrading enzyme affects postharvest softening in grape

The firmness of table grape berries is a crucial quality parameter. Despite extensive research on postharvest fruit softening, its precise molecular mechanisms remain elusive. To enhance our comprehension of the underlying molecular factors, we initially identified differentially expressed genes(DEGs) by comparing the transcriptomes of folic acid(FA)-treated and water-treated(CK) berries at different time points. We then analyzed the sequences to detect alternatively spliced(AS) genes associated with postharvest softening. A total of 2,559 DEGs were identified and categorized into four subclusters based on their expression patterns, with subcluster-4 genes exhibiting higher expression in the CK group compared with the FA treatment group. There were 1,045 AS-associated genes specific to FA-treated berries and 1,042 in the CK-treated berries, respectively. Gene Ontology(GO) annotation indicated that the AS-associated genes in CK-treated berries were predominantly enriched in cell wall metabolic processes,particularly cell wall degradation processes. Through a comparison between treatment-associated AS genes and subcluster-4 DEGs, we identified eight genes, including Pectinesterase 2(VvPE2, Vitvi15g00704), which encodes a cell wall-degrading enzyme and was predicted to undergo an A3SS event. The reverse transcription polymerase chain reaction further confirmed the presence of a truncated transcript variant of VvPE2 in the FA-treated berries.Our study provides a comprehensive analysis of AS events in postharvest grape berries using transcriptome sequencing and underscores the pivotal role of VvPE2 during the postharvest storage of grape berries.

Improved genome annotation of Brassica oleracea highlights the importance of alternative splicing

Brassica oleracea has been developed into many important crops,including cabbage,kale,cauliflower,broccoli and so on.The genome and gene annotation of cabbage(cultivar JZS),a representative morphotype of B.oleracea,has been widely used as a common reference in biological research.Although its genome assembly has been updated twice,the current gene annotation still lacks information on untranslated regions(UTRs)and alternative splicing(AS).Here,we constructed a high-quality gene annotation(JZSv3)using a full-length transcriptome acquired by nanopore sequencing,yielding a total of 59452 genes and 75684 transcripts.Additionally,we re-analyzed the previously reported transcriptome data related to the development of different tissues and cold response using JZSv3 as a reference,and found that 3843 out of 11908 differentially expressed genes(DEGs)underwent AS during the development of different tissues and 309 out of 903 cold-related genes underwent AS in response to cold stress.Meanwhile,we also identified many AS genes,including BolLHCB5 and BolHSP70,that displayed distinct expression patterns within variant transcripts of the same gene,highlighting the importance of JZSv3 as a pivotal reference for AS analysis.Overall,JZSv3 provides a valuable resource for exploring gene function,especially for obtaining a deeper understanding of AS regulation mechanisms.

Image Splicing Forgery Detection Using Feature-Based of Sonine Functions and Deep Features

The growing prevalence of fake images on the Internet and social media makes image integrity verification a crucial research topic.One of the most popular methods for manipulating digital images is image splicing,which involves copying a specific area from one image and pasting it into another.Attempts were made to mitigate the effects of image splicing,which continues to be a significant research challenge.This study proposes a new splicing detectionmodel,combining Sonine functions-derived convex-based features and deep features.Two stages make up the proposed method.The first step entails feature extraction,then classification using the“support vector machine”(SVM)to differentiate authentic and spliced images.The proposed Sonine functions-based feature extraction model reveals the spliced texture details by extracting some clues about the probability of image pixels.The proposed model achieved an accuracy of 98.93% when tested with the CASIA V2.0 dataset“Chinese Academy of Sciences,Institute of Automation”which is a publicly available dataset for forgery classification.The experimental results show that,for image splicing forgery detection,the proposed Sonine functions-derived convex-based features and deep features outperform state-of-the-art techniques in terms of accuracy,precision,and recall.Overall,the obtained detection accuracy attests to the benefit of using the Sonine functions alongside deep feature representations.Finding the regions or locations where image tampering has taken place is limited by the study.Future research will need to look into advanced image analysis techniques that can offer a higher degree of accuracy in identifying and localizing tampering regions.

2,3,5,4’-Tetrahydroxystilbene-2-O-b-D-Glucoside modulates CHEK2 and CCND1 alternative splicing to inhibit MCF-7 cells proliferation

Background:In our previous study,we observed a synergistic effect of 2,3,5,4’-Tetrahydroxystilbene-2-O-b-D-glucoside combined with adriamycin to induce apoptosis in MCF-7 breast cancer cells.However,the underlying mechanisms of epigenetic modifications,such as alternative splicing,have not been explored.In this study,we aimed to investigate the mechanism by which THSG inhibits MCF-7 cell proliferation using full-length transcriptome sequencing.Methods:First,cell viability was examined using the methyl thiazolyl tetrazolium method and full-length transcriptome sequencing was performed to identify genes and pathways.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used to identify the principal pathways and targets of THSG.Flow cytometry analysis of cell cycle distribution was performed.Meanwhile,the analysis of alternative splicing and domains of the key proteins was conducted.Quantitative polymerase chain reaction and western blotting were performed for verification.Results:THSG showed significant cytotoxic activity in MCF-7 cells.Full-length transcriptome sequencing revealed differential alternative splicing with 173 upregulated and 263 downregulated genes.Further analysis identified distinct differential expression of genes(CHEK2-211 and CCND1-201)involved in the cell cycle in the THSG-treated group.Subsequently,alternative splicing types of CHEK2(mutually exclusive exon)and CCND1(intron retention).We found that THSG downregulated mRNA expression,as confirmed by quantitative polymerase chain reaction analysis.Interestingly,protein structural analysis revealed that THSG treatment led to the generation of CHK2-211,which was the result of a mutation in the amino acid residues(GLU-150,ASN-151)of the CHEK2 domain(VAL-150,GLY-151).and CyclinD1-201 were obtained when an amino acid(ASP-267)in the domain was lost in CyclinD1.Moreover,molecular docking analysis demonstrated that the domains of key proteins could bind THSG more effectively,with no difference in affinity.Western blotting confirmed that THSG inhibited the expression of CHK2 and CyclinD1.Conclusion:THSG modulated the alternative splicing of CHEK2 and CCND1 by inducing G0/G1 cell cycle arrest,consequently suppressing MCF-7 cell proliferation.

Tension Active Disturbance Rejection Control of Automatic Yarn Splicing Robots for Ring Spinning

Automatic splicing of interrupted yarns in ring spinning has always been a problem in the industry.Factors such as low yarn strengths and environmental influence on yarn tensions make it difficult to control the yarn tension during the robotic splicing process.The purpose of this research is to design active disturbance rejection control(ADRC)for a third-order nonlinear tension system subject to external disturbances.Firstly,a third-order extended state observer(ESO)is designed to achieve the suppression and the compensation of the internal modeling error and the external disturbances of the system.Secondly,the adaptive gain error feedback control and the filtering process are designed to reduce the influence of sensor noise on the disturbance observation.Finally,the tension control during the splicing process is simulated and experimented,and the experiments show that the method has good robustness in the tension tracking task under a dynamic environment,which verifies the effectiveness of the method.

Analysis of Roadbed Splicing at Hub Interchanges

This article discusses the roadbed splicing for hub interchanges.The article starts with a description of the characteristics of junction roadbed splicing.The application of splicing technology is explained using a subgrade splicing scheme of a project.Roadbed splicing involves stepwise excavation and preparative measures like surface cleaning and backfilling.This article serves to provide a valuable reference for road and bridge construction and improve the quality of China’s road and bridge projects,so as to achieve sustainable development of the road and bridge engineering industry.

Splicing factor proline and glutamine-rich is a prognostic biomarker and correlated with clinical pathologic features and immune infiltrates in hepatocellular carcinoma

Background:Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-related deaths globally.Splicing factor proline and glutamine-rich(SFPQ)is a multifunctional protein that controls various biological functions.As a potential therapeutic target and a promising prognostic indicator,the potential effects and processes of SFPQ in HCC require further investigation.Methods:The RNA sequencing data were obtained from the Gene Expression Omnibus,International Cancer Genome Consortium,and The Cancer Genome Atlas databases to analyze SFPQ expression and differentially expressed genes(DEGs).We utilized the LinkedOmics database to identify co-expressed genes.A Venn diagram was constructed to determine the overlapping genes between the DEGs and the co-expressed genes.Functional enrichment analysis was performed on the overlapping genes and DEGs.Furthermore,our study involved functional enrichment analysis,a protein-protein interaction network analysis,and an analysis of immune cell infiltration.The cBioPortal and Tumor Immune Single-cell Hub were utilized to investigate the genetic alterations of SFPQ and the single-cell transcriptome visualization of the tumor microenvironment.A ceRNA network was established with the assistance of the ENCORI website.Finally,we elucidated the clinical significance of SFPQ in HCC by employing Kaplan-Meier survival analysis,univariate and multivariate Cox regression,and prognostic nomogram models.Results:The expression of SFPQ in HCC tissues was significantly elevated compared to normal tissues.GSEA results indicated that increased expression of SFPQ was associated with pathways related to HCC.The ceRNA network,including SFPQ,hsa-miR-101-3p,AC023043.4,AC124798.1,AC145207.5,and GSEC,was constructed with the assistance of ENCORI.High SFPQ expression was related to a poor prognosis in HCC and its subtypes.Univariate and multivariate Cox regression analysis showed that elevated SFPQ expression is an independent predictive factor.Conclusions:The overexpression of SFPQ may serve as a potential prognostic biomarker,indicating a poor prognosis in HCC.

Impairment of pre-mRNA splicing in liver disease: Mechanisms and consequences

Pre-mRNA splicing is an essential step in the process of gene expression in eukaryotes and consists of the removal ofintrons and the linking of exons to generate mature mRNAs. This is a highly regulated mechanism that allows the alternative usage of exons, the retention ofintronic sequences and the generation of exonic sequences of variable length. Most human genes undergo splicing events, and disruptions of this process have been associated with a variety of diseases, including cancer. Hepatocellular carcinoma (HCC) is a molecularly heterogeneous type of tumor that usually develops in a cirrhotic liver. Alterations in pre-mRNA splicing of some genes have been observed in liver cancer, and although still scarce, the available data suggest that splicing defects may have a role in hepatocarcinogenesis. Here we briefly review the general mechanisms that regulatepre-mRNA splicing, and discuss some examples that illustrate how this process is impaired in liver tumorigenesis, and may contribute to HCC development. We believe that a more thorough examination of pre-mRNA splicing is still needed to accurately draw the molecular portrait of liver cancer. This will surely contribute to a better understanding of the disease and to the development of new effective therapies.

NOVA1 promotes SMN2 exon 7 splicing by binding the UCAC motif and increases SMN protein expression

Spinal muscular atrophy(SMA)is a rare hereditary neuromuscular disease with a high lethality rate in infants.Variants in the homologous genes survival of motor neuron(SMN)1 and SMN2 have been reported to be SMA pathogenic factors.Previous studies showed that a highinclusion rate of SMN2 exon 7 increased SMN expression,which in turn reduced the severity of SMA.The inclusion rate of SMN2 exon 7 was higher in neural tissues than in non-neural tissues.Neuro-oncological ventral antigen(NOVA)is a splicing factor that is specifically and highly expressed in neurons.It plays a key role in nervous system development and in the induction of nervous system diseases.Howeve r,it remains unclear whether this splicing factor affects SMA.In this study,we analyzed the inclusion of SMN2 exon 7 in different tissues in a mouse model of SMA(genotype smn^(-/-)SMN2^(2 tg/0))and litter mate controls(genotype smn^(+/-)SMN2^(2 tg/0)).We found that inclusion level of SMN2 exon 7 was high in the brain and spinal co rd tissue,and that NOVA1 was also highly expressed in nervous system tissues.In addition,SMN2 exon 7 and NOVA1 were expressed synchronously in the central nervous system.We further investigated the effects of NOVA1 on disease and found that the number of neurons in the anterior horn of spinal cord decreased in the mouse model of SMA during postnatal days 1-7,and that NOVA1 expression levels in motor neurons decreased simultaneously as spinal muscular atrophy developed.We also found that in vitro expression of NOVA1 increased the inclusion of SMN2 exon 7 and expression ofthe SMN2 protein in the U87 MG cell line,whereas the opposite was observed when NOVA1 was knocked down.Finally,point mutation and RNA pull-down showed that the UCAC motif in SMN2 exon 7 plays a critical role in NOVA1 binding and promoting the inclusion of exon 7.Moreove r,CA was more essential for the inclusion of exon 7 than the order of Y residues in the motif.Collectively,these findings indicate that NOVA1 intera cts with the UCAC motif in exon 7 of SMN2,there by enhancing inclusion of exon 7 in SMN2,which in turn increases expression of the SMN protein.

Identification of global alternative splicing and sex-specific splicing via comparative transcriptome analysis of gonads of Chinese tongue sole(Cynoglossus semilaevis)

Chinese tongue sole(Cynoglossus semilaevis)is an economically important marine fish species with a ZZ/ZW sex determination mechanism,which can be influenced by temperature.Alternative splicing(AS)is an important mechanism regulating the expression of genes related to sex determination and gonadal differentiation,but has rarely been reported in fish.In this study,to explore the molecular regulatory mechanisms of sex determination and gonadal differentiation,we combined isoform and RNA sequencing(Iso-Seq and RNA-Seq)to perform transcriptome profiling of male and female gonads in C.semilaevis.In total,81883 and 32341 full-length transcripts were obtained in males and females,respectively.A total of 8279 AS genes were identified,including 2639 genes showing differential AS(DAS)between males and females.Many intersecting DAS genes and differentially expressed genes(DEGs)were enriched in the meiotic cell cycle pathway,and genes related to gonadal differentiation,such as esrrb and wt1a,were found to have sex-specific isoforms.Thus,this study revealed AS events in the gonadal transcriptomes of male and female C.semilaevis,described the characteristics of active transcription in the testes,and identified candidate genes for studying the regulatory mechanisms of AS during gonadal differentiation.

Splicing Image and Its Localization:A Survey

With the rapid development of information technology,digital images have become an important medium for information transmission.However,manipulating images is becoming a common task with the powerful image editing tools and software,and people can tamper the images content without leaving any visible traces of splicing in order to gain personal goal.Images are easily spliced and distributed,and the situation will be a great threat to social security.The survey covers splicing image and its localization.The present status of splicing image localization approaches is discussed along with a recommendation for future research.

Serine and arginine rich splicing factor 1:a potential target for neuroprotection and other diseases

Alternative splicing is the process of producing variably spliced mRNAs by choosing distinct combinations of splice sites within a messenger RNA precursor.This splicing enables mRNA from a single gene to synthesize different proteins,which have different cellular properties and functions and yet arise from the same single gene.A family of splicing factors,Serine-arginine rich proteins,are needed to initiate the assembly and activation of the spliceosome.Serine and arginine rich splicing factor 1,part of the arginine/serine-rich splicing factor protein family,can either activate or inhibit the splicing of mRNAs,depending on the phosphorylation status of the protein and its interaction partners.Considering that serine and arginine rich splicing factor 1 is either an activator or an inhibitor,this protein has been studied widely to identify its various roles in different diseases.Research has found that serine and arginine rich splicing factor 1 is a key target for neuroprotection,showing its promising potential use in therapeutics for neurodegenerative disorders.Furthermore,serine and arginine rich splicing factor 1 might be used to regulate cancer development and autoimmune diseases.In this review,we highlight how serine and arginine rich splicing factor 1 has been studied concerning neuroprotection.In addition,we draw attention to how serine and arginine rich splicing factor 1 is being studied in cancer and immunological disorders,as well as how serine and arginine rich splicing factor 1 acts outside the central or peripheral nervous system.

Dynamic regulation of alternative splicing and chromatin structure in Drosophila gonads revealed by RNA-seq

Both transcription and post-transcriptional processes, such as alternative splicing, play crucial roles in controlling developmental programs in metazoans. Recently emerged RNA-seq method has brought our understanding of eukaryotic transcriptomes to a new level, because it can resolve both gene expression level and alternative splicing events simultaneously. To gain a better understanding of cellular differentiation in gonads, we analyzed mRNA profiles from Drosophila testes and ovaries using RNA-seq. We identified a set of genes that have sex-specific isoforms in wild-type （WT） gonads, including several transcription factors. We found that differentiation of sperms from undifferentiated germ cells induced a dramatic downregulation of RNA splicing factors. Our data confirmed that RNA splicing events are significantly more frequent in the undifferentiated cell-enriched bag of marbles （barn） mutant testis, but downregulated upon differentiation in WT testis. Consistent with this, we showed that genes required for meiosis and terminal differentiation in WT testis were mainly regulated at the transcriptional level, but not by alternative splicing. Unexpectedly, we observed an increase in expression of all families of chromatin remodeling factors and histone modifying enzymes in the undifferentiated cell-enriched bam testis. More interestingly, chromatin regulators and histone modifying enzymes with opposite enzymatic activities are coenriched in undifferentiated cells in testis, suggesting that these cells may possess dynamic chromatin architecture. Finally, our data revealed many new features of the Drosophila gonadal transcriptomes, and will lead to a more comprehensive understanding of how differential gene expression and splicing regulate gametogenesis in Drosophila. Our data provided a foundation for the systematic study of gene expression and alternative splicing in many interesting areas of germ cell biology in Droso- phila, such as the molecular basis for sexual dimorphism and the regulation of the proliferation vs terminal differentiation programs in germline stem cell lineages. The GEO accession number for the raw and analyzed RNA-seq data is GSE16960.

Allele-specific expression and alternative splicing in horse×donkey and cattle×yak hybrids

Divergence of gene expression and alter native splicing is a crucial driving force in the evolution of species;to date, however the molecular mechanism remains unclear. Hybrids of closely related species provide a suitable model to analyze allele-specific expressi on (ASE) and allele-specific alter native splicing (ASS). Analysis of ASE and ASS can uncover the differences in cis-regulatory elements between closely related species, while eliminating interferenee of trans-regulatory elements. Here, we provide a detailed characterization of ASE and ASS from 19 and 10 transcriptome datasets across five tissues from reciprocal-cross hybrids of horsex don key (mule/hi nny) and cattlexyak (dzo), respectively. Results showed that 4.8%-8.7% and 10.8%-16.7% of genes exhibited ASE and ASS, respectively. Notably, IncRNAs and pseudogenes were more likely to show ASE than protein-coding genes. In addition, genes showing ASE and ASS in mule/hinny were found to be involved in the regulation of muscle strength, whereas those of dzo were involved in high-altitude adaptati on. In con clusi on, our study dem on strated that explorati on of genes showing ASE and ASS in hybrids of closely related species is feasible for species evolution research.

Heat Stress Upregulates the Expression of TLR4 and Its Alternative Splicing Variant in Bama Miniature Pigs

Alternative splicing is a cellular mechanism in eukaryotes that results in considerable diversity ofgene products. It plays an important role in several diseases and cellular signal regulation. Heat stress is a major factor that induces immunosuppression in pigs. Little is known about the correlation between alternative splicing and heat stress in pigs. Therefore, this study aimed to clone, sequence and quantify the alternative splicing variant of toll-like receptor 4 （TLR4） in Bama miniature pigs （Sus scrofa domestica） following exposure to heat stress. The results showed that the second exon of TLR4 was spliced and 167 bp shorter in the alternative splicing variant, and the protein was putatively identified as a type of truncated membrane protein consisting of extramembrane, transmembrane and intramembrane regions lacking a signal peptide. Further, it was not a non- classical secretory protein. Five potential reference genes were screened for their potential as reliable standards to quantify the expression of TLR4 alternative spliced variants by real-time quantitative reverse-transcriptase polymerase chain reaction （qRT-PCR）. The stability of these reference genes was ranked using the geNorm and NormFinder programs, and ribosomal protein L4 （RPL4） and TATA box-binding protein （TBP） were found to be the two genes showing the most stable expression in the in vitro cultured peripheral blood mononuclear ceils （PBMCs） during heat shock. The mRNA level of the TLR4 gene （both classical and spliced） in stressed pigs increased significantly （P〈0.05）. Further, the expression levels of the alternative spliced variant of TLR4 （TLR4-ASV） showed a 2-3 folds increase in heat-stressed PBMCs as compared to control pigs. The results of the present study suggested that heat shock might modulate the host immune response by regulating the expressions of TLR4 and its alternative splicing variant.

Alternative splicing of VEGFA,APP and NUMB genes in colorectal cancer

AIM:To investigate alternative splicing in vascular endothelial growth factor A(VEGFA),amyloid beta precursor protein(APP),and Numb homolog(NUMB) in colorectal cancer(CRC).METHODS:Real-time quantitative reverse transcriptase polymerase chain reaction(q RT-PCR) and PCRrestriction fragment length polymorphism analyses were performed to detect the expression of VEGFA,APP,and NUMB mR NA in 20 CRC tissues and matched adjacent normal tissues,as well as their alternative splicing variants.RESULTS:q RT-PCR analysis revealed that the expression of APP,NUMB,and VEGFA 165 b m RNA were significantly downregulated,while VEGFA m RNA was upregulated,in CRC tissues(all P < 0.05).PCRrestriction fragment length polymorphism analysis revealed that the expression of VEGFA 165a/b in CRC tissues was significantly higher than in adjacent normal tissues(P < 0.05).Compared with adjacent normal tissues,the expression of NUMB-PRRS in CRC tissues was significantly decreased(P < 0.05),and the expression of NUMB-PRRL was increased(P < 0.05).CONCLUSION:Alternative splicing of VEGFA,APP,and NUMB may regulate the development of CRC,and represent new targets for its diagnosis,prognosis,and treatment.

Alterations of Alternative Splicing Patterns of Ser/Arg-Rich (SR) Genes in Response to Hormones and Stresses Treatments in Different Ecotypes of Rice (Oryza sativa)

Ser/Arg-rich （SR） genes encode proteins that play pivotal roles in both constitutive and alternative splicing of pre-mRNA. However, not much effort has been made to investigate the alternative splicing of their own pre-mRNA. In this study, we conducted comprehensive analyses of pre-mRNA splicing for 22 SR genes in three rice （Oryza sativa L.） ecotypes indica, japonica andjavanica. Using different ecotypes we characterized the variations in expression and splicing patterns of rice SR genes in different tissues and at different developmental stages. In addition, we compared the divergence in expression and splicing patterns of SR genes from seedlings of different rice ecotypes in response to hormones application and environmental stresses. Our results revealed the complexity of alternative splicing of SR genes in rice. The splicing varies in different tissues, in different ecotypes, in response to stresses and hormones. Thus, our study suggested that SR genes were subjected to sophisticated alternative splicing although their encoding proteins were involved in the splicing process.