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Molecular characteristics and clinical implications of serine/arginine-rich splicing factors in human cancer.

ABSTRACT: As critical splicing regulators, serine/arginine-rich splicing factors (SRSFs) play pivotal roles in carcinogenesis. As dysregulation of SRSFs may confer potential cancer risks, targeting SRSFs could provide important insights into cancer therapy. However, a global and comprehensive pattern to elaborate the molecular characteristics, mechanisms, and clinical links of SRSFs in a wide variety of human cancer is still lacking. In this study, a systematic analysis was conducted to reveal the molecular characteristics and clinical implications of SRSFs covering more than 10000 tumour samples of 33 human cancer types. We found that SRSFs experienced prevalent genomic alterations and expression perturbations in multiple cancer types. The DNA methylation, m6A modification, and miRNA regulation of SRSFs were all cancer context-dependent. Importantly, we found that SRSFs were strongly associated with cancer immunity, and were capable of predicting response to immunotherapy. And SRSFs had colossal potential for predicting survival in multiple cancer types, including those that have received immunotherapy. Moreover, we also found that SRSFs could indicate the drug sensitivity of targeted therapy and chemotherapy. Our research highlights the significance of SRSFs in cancer occurrence and development, and provides sufficient resources for understanding the biological characteristics of SRSFs, offering a new and unique perspective for developing cancer therapeutic strategies.

SUBMITTER: Zhang J

PROVIDER: S-EPMC10713412 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Molecular characteristics and clinical implications of serine/arginine-rich splicing factors in human cancer.

Zhang Jinjin J Fang Zhicheng Z Song Congkuan C

Aging 20231124 22

As critical splicing regulators, serine/arginine-rich splicing factors (SRSFs) play pivotal roles in carcinogenesis. As dysregulation of SRSFs may confer potential cancer risks, targeting SRSFs could provide important insights into cancer therapy. However, a global and comprehensive pattern to elaborate the molecular characteristics, mechanisms, and clinical links of SRSFs in a wide variety of human cancer is still lacking. In this study, a systematic analysis was conducted to reveal the molecul ...[more]

PMID: 38015716

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Project description:BackgroundDysregulated splicing events are a common phenomenon in cancer with the Serine-arginine-rich splicing factor (SRSF) family emerging as pivotal regulators of gene expression, exerting influence over constitutive and alternative splicing processes. Although aberrations in a few SRSF family members have been implicated in various cancers, the comprehensive roles of other family constituents remain underexplored.MethodsThis study delves into the expression profile of the entire SRSF family (SRSF1-SRSF12) in 23 cancerous cell lines originating from diverse tissues using quantitative Real-Time PCR. Further, the transcript levels of the SRSF family were examined in oral cancer patient samples stratified into Pre-cancer (n = 15), Early cancer (n = 11), Late cancer (n = 14), and adjacent non-tumor tissues (n = 26) as controls. The results were corroborated by a parallel investigation utilizing the transcriptomics data of oral squamous cell carcinoma (OSCC) patients (n = 319) and controls (n = 35) available in The Cancer Genome Atlas (TCGA) database.ResultsOur investigation reveals a notable upregulation in the expression levels of key splicing factors, namely SRSF3, SRSF9, and SRSF10 in all oral cancer cell lines (SCC-4, UM-SCC-84, CAL33, SAS-H1). Conversely, no significant associations between SRSF family members and other cancer cell lines were discerned. Further, the expression profile of the SRSF family in oral cancer patient samples revealed significant upregulation of SRSF1, SRSF3, SRSF7, SRSF9, SRSF10, and SRSF11 in patients with late-stage oral cancer compared to controls. Transcriptomics data from TCGA database demonstrated remarkable upregulation of SRSF1, SRSF4, SRSF9, SRSF10, and SRSF11 in OSCC patients.ConclusionCollectively our results underscore the critical involvement of SRSF family members in the context of oral cancer, highlighting their potential as key players in the altered splicing dynamics associated with cancer progression.

Dataset Information

Molecular characteristics and clinical implications of serine/arginine-rich splicing factors in human cancer.

Publications

Molecular characteristics and clinical implications of serine/arginine-rich splicing factors in human cancer.

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