Biological function and molecular mechanism of SRSF3 in cancer and beyond (Review)

Xiong, Jian; Chen, Yinshuang; Wang, Weipeng; Sun, Jing

doi:10.3892/ol.2021.13139

Cited by 11 publications

(10 citation statements)

References 108 publications

(156 reference statements)

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“…2E , left and right). Among these genes, we identified members encoding (i) a family encoding serine/arginine-rich splicing factors that play roles in RNA metabolism, including alternative splicing and intron retention [ 23 , 24 ] (Fig. 2F ), and (ii) the SWI/SNF BAF and PBAF chromatin remodeling complexes, which have been linked to MUC1-C-induced progression of prostate carcinoma cells [ 14 , 25 ] (Fig.…”

Section: Resultsmentioning

confidence: 99%

Addiction of Merkel cell carcinoma to MUC1-C identifies a potential new target for treatment

et al. 2022

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Merkel cell carcinoma (MCC) is an aggressive malignancy with neuroendocrine (NE) features, limited treatment options, and a lack of druggable targets. There is no reported involvement of the MUC1-C oncogenic protein in MCC progression. We show here that MUC1-C is broadly expressed in MCCs and at higher levels in Merkel cell polyomavirus (MCPyV)-positive (MCCP) relative to MCPyV-negative (MCCN) tumors. Our results further demonstrate that MUC1-C is expressed in MCCP, as well as MCCN, cell lines and regulates common sets of signaling pathways related to RNA synthesis, processing, and transport in both subtypes. Mechanistically, MUC1-C (i) interacts with MYCL, which drives MCC progression, (ii) is necessary for expression of the OCT4, SOX2, KLF4, MYC, and NANOG pluripotency factors, and (iii) induces the NEUROD1, BRN2 and ATOH1 NE lineage dictating transcription factors. We show that MUC1-C is also necessary for MCCP and MCCN cell survival by suppressing DNA replication stress, the p53 pathway, and apoptosis. In concert with these results, targeting MUC1-C genetically and pharmacologically inhibits MCC self-renewal capacity and tumorigenicity. These findings demonstrate that MCCP and MCCN cells are addicted to MUC1-C and identify MUC1-C as a potential target for MCC treatment.

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Section: Resultsmentioning

confidence: 99%

Addiction of Merkel cell carcinoma to MUC1-C identifies a potential new target for treatment

et al. 2022

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“…Notably, the SRSF3 genes in the gut showed signi cant negative correlations with factors 1 and 2. According to recent studies, SRSF3 suppresses tumorigenesis 54 and inhibits cellular senescence 55 . Thus, reduced SRSF3 expression might be an important contributor to gastrointestinal dysfunction caused by SD and an HFD.…”

Section: Integration Analysis Of Gut Microbiome and Host Gene Expressionmentioning

confidence: 99%

Integrated analysis of the microbiota-gut-brain axis in response to sleep deprivation in a diet-induced obesity mouse model

Lee

Kang

et al. 2022

Preprint

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Sleep deprivation (SD) and obesity are common in modern societies. SD and obesity frequently coexist, but research on the combined consequences of SD and obesity has been limited. In this study, we investigated the gut microbiota and host responses to SD and high-fat diet (HFD)-induced obesity. In addition, we attempted to identify key mediators of the microbiota-gut-brain axis. C57BL/6J mice were divided into four groups based on whether they were sleep deprived and whether they were fed a standard chow diet (SCD) or HFD. We then performed fecal microbiome shotgun sequencing, gut transcriptome analysis using RNA sequencing, and brain mRNA expression analysis using the nanoString nCounter Mouse Neuroinflammation Panel. The gut microbiota was significantly altered by the HFD, whereas the gut transcriptome was primarily influenced by SD. Sleep and diet are both important in the inflammatory system of the brain. When SD and the HFD were combined, the inflammatory system of the brain was severely disrupted. In addition, inosine-5' phosphate may be the gut microbial metabolite that mediates microbiota-gut-brain interactions. To identify the major drivers of this interaction, we analyzed the multi-omics data. Integrative analysis revealed two driver factors that were mostly composed of the gut microbiota. We discovered that the gut microbiota may be the primary driver of microbiota-gut-brain interactions. These findings imply that healing gut dysbiosis may be a viable therapeutic target for enhancing sleep quality and curing obesity-related dysfunction.

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“…Although most human internal exons are between 50 to 200 nucleotides (nt) in length ( 18 ), 5% are exons longer than 1000 nt, are evolutionarily conserved across mammals, and are mostly expressed and translated ( 19 ). The SRS3 splicing factor promotes the inclusion of large exons enriched with C-nucleotides in vertebrates ( 20 ) and plays important roles in the occurrence and development of tumors ( 21 ). Intriguingly, long exons in vertebrates frequently encode IDRs ( 20 ).…”

Section: Main Textmentioning

confidence: 99%

“…The SRSF3 splicing factor promotes the inclusion of large exons enriched with C-nucleotides in vertebrates (Kawachi et al 2021) and plays important roles in the occurrence and development of tumours (Xiong et al 2022). Intriguingly, long exons in vertebrates frequently encode IDRs (Kawachi et al 2021).…”

Section: Introductionmentioning

confidence: 99%

Exon Elongation Added Intrinsically Disordered Regions to the Encoded Proteins and Facilitated the Emergence of the Last Eukaryotic Common Ancestor

Homma¹,

Fukuch

Noguchi³

et al. 2022

Preprint

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Most prokaryotic proteins consist of one structural domain (SD), while a typical eukaryotic protein is comprised of multiple SDs and intrinsically disordered regions (IDRs) that by themselves do not adopt stable structures. In eukaryotes IDRs are especially prevalent in transcription factors and are involved in condensates that regulate diverse cellular functions. How eukaryotic proteins evolved to differ from prokaryotic proteins has not been fully elucidated. Here we find that the longer internal exons are, the more frequently they encode IDRs in general. Moreover, the boundaries of long internal exons tend to fall outside of structural domains. These findings are consistent with the idea that some internal exons whose boundaries were aligned outside of structural domains acquired sections encoding IDRs. Most of the internal exon segments that probably lengthened after the rat-mouse divergence encode IDRs, supporting the view. We surmise that many exons whose boundaries were not aligned to the inside of structural domains elongated to add IDRs to the encoded proteins, often conferring new functions. Some of the IDRs possibly served as spacers in acquiring structural domains through recombination. We propose that the "small bang" that lengthened exons facilitated the evolution that led to the last common ancestor of eukaryotes.

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Biological function and molecular mechanism of SRSF3 in cancer and beyond (Review)

Cited by 11 publications

References 108 publications

Addiction of Merkel cell carcinoma to MUC1-C identifies a potential new target for treatment

Addiction of Merkel cell carcinoma to MUC1-C identifies a potential new target for treatment

Integrated analysis of the microbiota-gut-brain axis in response to sleep deprivation in a diet-induced obesity mouse model

Exon Elongation Added Intrinsically Disordered Regions to the Encoded Proteins and Facilitated the Emergence of the Last Eukaryotic Common Ancestor

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