An alternatively spliced p62 isoform promotes breast cancer chemoresistance
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ABSTRACT:
PROVIDER: PRJNA812680 | ENA |
REPOSITORIES: ENA
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Project description:Chemoresistance remains a major obstacle to the successful treatment of breast cancer. Especially, more than 80% of cases cannot achieve pathological complete response (pCR) in patients who received neoadjuvant chemotherapy (NAC). Understanding the mechanisms involved in chemoresistance can guide the development of efficient therapies in patients with breast cancer. Herein, we identified a novel p62 isoform with a short 3′UTR (p62-SU, 662-nt) that is associated with chemoresistance by RNA-sequence and verified by qRT-PCR, 3′RACE, and northern blot in breast cancer cells and tissue specimens. Furthermore, enforced expression of p62-SU dramatically promoted the ability of proliferation, migration, invasion, and chemoresistance compared with p62 isoform with a long/full-length 3′UTR (p62-LU, 1485-nt) in vivo and in vitro. Mechanistically, we revealed that CPSF1 could regulate the 3′UTR shorting of p62 by alternative polyadenylation and then enhanced chemoresistance in breast cancer cells. In addition, we found that p62-SU escaped the repression of miR-124-3p and promoted the ability of p62-SU to produce more protein and, subsequently, p62-dependent chemoresistance. Together, our data suggest the p62-SU, generated by CPSF1, plays an essential role in the regulation of breast cancer chemoresistance through CPSF1-p62-miR-124-3p signaling.
2022-03-06 | GSE197894 | GEO
Project description:Alternative splicing of mRNA diversifies the function of human proteins, with tissue- and cell-specific protein isoforms being the most difficult to validate. While transcriptomic experiments enable the detection of many alternatively spliced transcripts, it is not known if these transcripts have protein-coding potential. We recently published the PG Nexus pipeline, which facilitates high confidence validation of exons and exon-exon junctions of spliced transcripts by integrating transcriptomics and proteomics data. Using the PG Nexus, we analyzed undifferentiated human mesenchymal stem cells and compared the number of protein isoforms validated using different protein sequence database, including public online databases and RNA-seq derived databases. With significant overlaps with other databases, we identified 8,011 exons and 3,824 splice junctions with the Ensembl database. Both exonic and junction peptides were important for protein isoform validation. The Ensembl database consistently outperformed the other data sources, but predicted open reading frames from RNA-seq derived transcripts were comparable, with only 6 less splice junctions validated. Using proteotypic and isoform-specific peptides, we validated 462 protein isoforms. This number increases to 1,083 if multiple proteotypic peptides per protein are included. Multiplexing proteotypic peptides in SRM assays or similar experiments will increase the confidence and coverage of protein isoform validation experiments.
2015-05-20 | PXD001449 | Pride
Project description:Glycine max Alternatively Spliced Transcript Detecting Microarray (GmASDM).
| PRJNA643563 | ENA
Project description:Systematic mutagenesis has revealed that synonymous, non-synonymous and intronic mutations frequently alter the inclusion levels of alternatively spliced exons, suggesting that altered splicing might be a common mechanism by which mutations cause disease. However, most exons expressed in any cell are highly-included in mature mRNAs. Here, by performing deep mutagenesis of highly-included exons and by analysing the association between sequence variation and exon inclusion across the genome, we report that mutations only very rarely alter the inclusion of highly-included exons. This is true for both exonic and intronic mutations as well as for perturbations in trans. Therefore, mutations that affect splicing are not evenly distributed across the genome but are focussed in and around alternatively spliced exons with intermediate inclusion levels. These results provide a resource for prioritising synonymous and other variants as disease-causing mutations.
2020-06-29 | GSE151942 | GEO
Project description:Mutations primarily alter the inclusion of alternatively spliced exons
| PRJNA637776 | ENA
Project description:The Drosophila melanogaster gene Dscam can generate thousands of different ectodomains via mutual exclusive splicing of three large exon clusters. The isoform diversity plays a profound role in both neuronal wiring and pathogen recognition. However, it remained unexplored how many isoforms are indeed expressed, whether the splicing choice between the clusters is independent and why the diversity encoded in the gene locus seems to be beyond necessity. To address these questions, we developed IsomSeq, a novel multiple segment sequencing method that allows to directly quantify the alternatively spliced exon combination of Dscam isoforms within an entire cellular and organismal transcriptome.
2013-06-27 | GSE45167 | GEO
Project description:The Drosophila melanogaster gene Dscam can generate thousands of different ectodomains via mutual exclusive splicing of three large exon clusters. The isoform diversity plays a profound role in both neuronal wiring and pathogen recognition. However, it remained unexplored how many isoforms are indeed expressed, whether the splicing choice between the clusters is independent and why the diversity encoded in the gene locus seems to be beyond necessity. To address these questions, we developed IsomSeq, a novel multiple segment sequencing method that allows to directly quantify the alternatively spliced exon combination of Dscam isoforms within an entire cellular and organismal transcriptome. We sequenced the dscam repertoire of adult brain, S2 cell line, and 5 different developmental stages (embryo, L1, L2, L3, pupa)
2013-06-27 | E-GEOD-45167 | biostudies-arrayexpress
Project description:The effects of alternatively spliced tissue factor (asTF) were measured by gene expression profiling of Capan-1 and Pt45P1 cells.
2013-04-10 | GSE45928 | GEO
Project description:The effects of alternatively spliced tissue factor (asTF) were measured by gene expression profiling of Capan-1 and Pt45P1 cells. 4 samples: Capan-1 cells +/- asTF, Pt45P1 cells +/- asTF.
2013-04-10 | E-GEOD-45928 | biostudies-arrayexpress
Project description:RNA splicing is a molecular mechanism to increase protein diversities acquired through the evolution while the underlieing driving forces for the phenomenon are unknown especially in terms of gene expression. Rice alternatively spliced transcript detecting microarray (ASDM) was designed and applied to differentiate the transcriptome of 4 representative organs of Oryza sativa L. cv. Ilmi including leaves, roots, panicles at 1 cm stage and young seeds at 20 days after pollination. The comparison of the data between the microarray and RNA-seq shows a ‘bell shape distribution’ and a strong co-lineation for highly expressed genes. The transcripts are classified according to the degree of organ enrichment using coefficient value (CV, the ratio of standard deviation to the mean values); highly variable (CVI), variable (CVII), and constitutive (CVIII) groups. The genes of highly variable group show the characteristics of the organs. The index of the portion of loci with alternatively spliced transcripts in a group (IAS) is designated for these CV groups and showed the higher value in the constitutive group. In addition, within a locus, a transcript with longer cds tends to be higher expressed and the spliced_intron is the most commonly found type of alternative splicing for the extended cds. Thus, constitutively expressed genes might be under evolutionary pressure toward alternative splicing that might have a longer cds. These data show that less resource consuming and better designed microarray might be a niche technology to test the transcriptome analysis including alternatively spliced transcripts in plants.
2017-01-01 | GSE87536 | GEO