A pan-cancer analysis of alternative splicing of splicing factors in 6904 patients

Cheng, Rui; Xiao, Lixing; Zhou, Wenyang; Jin, Xiyun; Xu, Zhaochun; Xu, Chang; Wang, Pingping; Luo, Meng; Wang, Mengyun; Ma, Kexin; Cao, Huimin; Huang, Yan; Lin, Xiaoyu; Pang, Fenglan; Li, Yiqun; Jiang, Qinghua

doi:10.1038/s41388-021-01947-7

Cited by 20 publications

(9 citation statements)

References 66 publications

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“…38 As a member of the pathway “Diseases of signal transduction by growth factor receptors,” alternative splicing of FGFR1 might also involve in OA. Intriguingly, the result in our study that splicing factors are susceptibility to splicing was also found in several other studies, 39,40 indicating that splicing of splice factors response to stress conditions may also function in OA process. In summary, these results showed that alternative splicing events changed in OA, which might also draw contribution to the onset and progression of OA.…”

Section: Alternative Splicing In Osteoarthritissupporting

confidence: 89%

Integrated Analysis of Transcriptome Changes in Osteoarthritis: Gene Expression, Pathways and Alternative Splicing

Wei

Wang

et al. 2023

CARTILAGE

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Objective Osteoarthritis (OA) is the most prevalent joint disease characterized by the degeneration of articular cartilage and the remodeling of its underlying bones, resulting in pain and loss of function in the knees and hips. As far as we know, no curative treatments are available except for the joint replacement. The precise molecular mechanisms which are involved in the degradation of cartilage matrix and development of osteoarthritis are still unclear. Design By analyzing RNA-seq data, we found the molecular changes at the transcriptome level such as alternative splicing, gene expression, and molecular pathways in OA knees cartilage. Results Expression analysis have identified 457 differential expressed genes including 266 up-regulated genes such as TNFSF15, ST6GALNAC5, TGFBI, ASPM, and TYM, and 191 down-regulated genes such as ADM, JUN, IRE2, PIGA, and MAFF. Gene set enrichment analysis (GSEA) analysis identified down-regulated pathways related to translation, transcription, immunity, PI3K/AKT, and circadian as well as disturbed pathways related to extracellular matrix and collagen. Splicing analysis identified 442 differential alternative splicing events within 284 genes in osteoarthritis, including genes involved in extracellular matrix (ECM) and alternative splicing, and TIA1 was identified as a key regulator of these splicing events. Conclusions These findings provide insights into disease etiology, and offer favorable information to support the development of more effective interventions in response to the global clinical challenge of osteoarthritis.

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Section: Alternative Splicing In Osteoarthritissupporting

confidence: 89%

Integrated Analysis of Transcriptome Changes in Osteoarthritis: Gene Expression, Pathways and Alternative Splicing

Wei

Wang

et al. 2023

CARTILAGE

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“…The recently updated OncoSplicing database focuses on identifying clinically relevant AS events in cancer development by conducting survival and differential analyses 21 . ASPN, a splicing-derived neoepitope database, has compiled a list of potential AS-derived neoepitopes found in 16 types of cancers 22 To expand the molecular determinants for cancer classification, herein we have analyzed differentially regulated AS events in molecular subtypes of cancer using TCGA data. To promote the discovery of AS events as biomarkers, we have developed a pan-cancer database named AS-CMC (Alternative Splicing for Cancer Molecular Classification).…”

Section: As-cmc: a Pan-cancer Database Of Alternative Splicing For Mo...mentioning

confidence: 99%

“…The recently updated OncoSplicing database focuses on identifying clinically relevant AS events in cancer development by conducting survival and differential analyses 21 . ASPN, a splicing-derived neoepitope database, has compiled a list of potential AS-derived neoepitopes found in 16 types of cancers 22 . However, these databases have focused on identifying cancer-specific alterations in AS, and the role of AS in cancer classification has not been systematically explored to date.…”

Section: Introductionmentioning

confidence: 99%

AS-CMC: a pan-cancer database of alternative splicing for molecular classification of cancer

Park

Lee

Chung

2022

Sci Rep

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Alternative splicing (AS) is a post-transcriptional regulation that leads to the complexity of the transcriptome. Despite the growing importance of AS in cancer research, the role of AS has not been systematically studied, especially in understanding cancer molecular classification. Herein, we analyzed the molecular subtype-specific regulation of AS using The Cancer Genome Atlas data and constructed a web-based database, named Alternative Splicing for Cancer Molecular Classification (AS-CMC). Our system harbors three analysis modules for exploring subtype-specific AS events, evaluating their phenotype association, and performing pan-cancer comparison. The number of subtype-specific AS events was found to be diverse across cancer types, and some differentially regulated AS events were recurrently found in multiple cancer types. We analyzed a subtype-specific AS in exon 11 of mitogen-activated protein kinase kinase 7 (MAP3K7) as an example of a pan-cancer AS biomarker. This AS marker showed significant association with the survival of patients with stomach adenocarcinoma. Our analysis revealed AS as an important determinant for cancer molecular classification. AS-CMC is the first web-based resource that provides a comprehensive tool to explore the biological implications of AS events, facilitating the discovery of novel AS biomarkers.

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“…The result is a transcript with different RNA regulatory elements (stability and translation efficiency) or protein coding sequences [ 5 ]. AS mainly uses or restricts specific splicing sites through the cooperative combination of different trans-splicing factors and various cis-regulatory elements in the transcript [ 6 ]. AS is involved in different developmental stages, tissue types and stress responses in mammals.…”

Section: Introductionmentioning

confidence: 99%

Interaction of a Novel Alternatively Spliced Variant of HSD11B1L with Parkin Enhances the Carcinogenesis Potential of Glioblastoma: Peiminine Interferes with This Interaction

Hong

Tsai

et al. 2023

Cells

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Glioblastoma (GBM) is a primary brain tumor of unknown etiology. It is extremely aggressive, incurable and has a short average survival time for patients. Therefore, understanding the precise molecular mechanisms of this diseases is essential to establish effective treatments. In this study, we cloned and sequenced a splice variant of the hydroxysteroid-like 11-β dehydrogenase 1 gene (HSD11B1L) and named it HSD11B1L-181. HSD11 B1L-181 was specifically expressed only in GBM cells. Overexpression of this variant can significantly promote the proliferation, migration and invasion of GBM cells. Knockdown of HSD11B1L-181 expression inhibited the oncogenic potential of GBM cells. Furthermore, we identified the direct interaction of parkin with HSD11B1L-181 by screening the GBM cDNA expression library via yeast two-hybrid. Parkin is an RBR E3 ubiquitin ligase whose mutations are associated with tumorigenesis. Small interfering RNA treatment of parkin enhanced the proliferative, migratory and invasive abilities of GBM. Finally, we found that the alkaloid peiminine from the bulbs of Fritillaria thunbergii Miq blocks the interaction between HSD11B1L-181 and parkin, thereby lessening carcinogenesis of GBM. We further confirmed the potential of peiminine to prevent GBM in cellular, ectopic and orthotopic xenograft mouse models. Taken together, these findings not only provide insight into GBM, but also present an opportunity for future GBM treatment.

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A pan-cancer analysis of alternative splicing of splicing factors in 6904 patients

Cited by 20 publications

References 66 publications

Integrated Analysis of Transcriptome Changes in Osteoarthritis: Gene Expression, Pathways and Alternative Splicing

Integrated Analysis of Transcriptome Changes in Osteoarthritis: Gene Expression, Pathways and Alternative Splicing

AS-CMC: a pan-cancer database of alternative splicing for molecular classification of cancer

Interaction of a Novel Alternatively Spliced Variant of HSD11B1L with Parkin Enhances the Carcinogenesis Potential of Glioblastoma: Peiminine Interferes with This Interaction

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