Spliceosome component SF3B1 as novel prognostic biomarker and therapeutic target for prostate cancer

Jiménez‐Vacas, Juan M.; Herrero‐Aguayo, Vicente; Gómez, Enrique Gómez; León‐González, Antonio J.; Sáez-Martínez, Prudencio; Alors‐Perez, Emilia; Fuentes-Fayos, Antonio C; Martínez-López, Ana; Sánchez‐Sánchez, Rafael; Serrano, Teresa González; López-Ruiz, Daniel; Requena-Tapia, M.J.; Castaño, Justo P.; Gahete, Manuel D.; Luque, Raúl M.

doi:10.1016/j.trsl.2019.07.001

Cited by 61 publications

(75 citation statements)

References 59 publications

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“…In addition, pladienolide B treatment decreases the expression of In1-Ghrelin, an oncogenic splice variant of Ghrelin, suggesting that SF3B1 or the SF3b complex associates with alternative splicing of Ghrelin. Supporting these findings, pladienolide B treatment is indicated to suppress the proliferation, survival and migration of prostate cancer cells [103]. Therefore, SF3B2, SF3B1 and the SF3b complex may be good candidates of therapeutic targets, and small chemicals inhibiting/modulating the SF3b complex might be promising for prostate cancer treatment.…”

Section: Sf3b Complexmentioning

confidence: 76%

“…Thus, small molecule inhibitors of SRPKs and CLKs could be promising for the therapies of those cancers. In addition, small compounds inhibiting/modulating the SF3b complex might be potential candidates as therapeutic drugs for those cancers [100][101][102][103]. Further studies on cancer-specific splicing regulation will provide new therapeutic targets and advance the development of new drugs.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, prostate cancer xenografts with SF3B2-overexpression are more sensitive to pladienolide B treatment [102]. SF3B1 is overexpressed in prostate tumors and associates with aggressive features of prostate cancers [103]. SF3B1 expression positively correlates with AR-V7 expression, and pladienolide B treatment decreases AR-V7 expression.…”

Section: Sf3b Complexmentioning

confidence: 99%

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Roles of Splicing Factors in Hormone-Related Cancer Progression

Takeiwa

Mitobe

Ikeda

et al. 2020

IJMS

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Splicing of mRNA precursor (pre-mRNA) is a mechanism to generate multiple mRNA isoforms from a single pre-mRNA, and it plays an essential role in a variety of biological phenomena and diseases such as cancers. Previous studies have demonstrated that cancer-specific splicing events are involved in various aspects of cancers such as proliferation, migration and response to hormones, suggesting that splicing-targeting therapy can be promising as a new strategy for cancer treatment. In this review, we focus on the splicing regulation by RNA-binding proteins including Drosophila behavior/human splicing (DBHS) family proteins, serine/arginine-rich (SR) proteins and heterogeneous nuclear ribonucleoproteins (hnRNPs) in hormone-related cancers, such as breast and prostate cancers.

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Section: Sf3b Complexmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Sf3b Complexmentioning

confidence: 99%

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Roles of Splicing Factors in Hormone-Related Cancer Progression

Takeiwa

Mitobe

Ikeda

et al. 2020

IJMS

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“…HNRNPA1 is one of the most abundant core proteins of heterogeneous nuclear ribonucleoproteins (hnRNP) complexes and plays a key role in the regulation of alternative splicing. SF3B1 is an outstanding pre-mRNA splicing factor due to its frequent cancer-associated mutations and targeting for drug therapy [22][23][24][25][26] . In the early stages of spliceosome assembly, SF3B1 orchestrates an ATP-dependent series of structural and compositional rearrangements among small nuclear ribonucleoprotein particles (snRNP) at the pre-mRNA splice sites that ultimately accomplishes the act of pre-mRNA splicing [22,27,28] , but its roles in CHD has not been shown.…”

Section: Discussionmentioning

confidence: 99%

The abnormal regulation of spliceosome may be a key factor for coronary heart disease: a simple bioinformatics analysis

Li¹,

Sheng²,

Chi³

2020

Preprint

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Background: Cardiovascular Diseases (CVDs) has become a major disease threatening human health. As the main species of CVDs, coronary heart disease (CHD) is becoming more and more common. The pathogenesis of CHD, especially at the molecular level, is not entirely clear up to now. Explaining the pathogenesis of CHD is particularly important for its treatment and prognosis. Biological database data analysis via bioinformatics has been an important method for studying gene expression strategy in multiple human disease. The aim of this study was to identify key different expressed genes (DEGs) in CHD and elucidate the biological process of it.Methods: A total of two published microarray datasets of CHD was downloaded from the Gene Expression Omnibus (GEO). Then, bioinformatics analyses including differentially expressed genes (DEGs) analysis, venn analysis, gene ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein and protein interaction (PPI) network construction was performed. Quantitative real-time polymerase chain reactions (RT-qPCR) were used to detect the expression levels of DEGs in CHD.Results: A total of 122 dysregulated genes were selected as DEGs in CHD. The GO annotation analysis displayed these DEGs involved in DNA transcription and mRNA splicing regulation. The DEGs regulatory network showed the downregulated genes LUC7L3, HNRNPA1, SF3B1, ARGLU1, SRSF5, SRSF11, SREK1, PNISR, DIDO1, ZRSR2 and NKTR were located in the network control center, which were the spliceosome related genes. The RT-qPCR results were consistent with our microarray analysis.Conclusion: The abnormal regulation of spliceosome might be a key factor in the development of CHD, which must play key roles in cardiovascular disease (CVD), especially in CHD. Our study has provided a new idea for the treatment and prognosis of CHD, and the spliceosome might be the potential prognostic biomarkers of it.

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“…All biopsy specimens were analyzed by experienced urologic pathologists according to the International Society of Urological Pathology 2005 modified criteria [14]. Tumor regions (n = 84) were identified from the Formalin-Fixed Paraffin-Embedded (FFPE) samples by expert urologic pathologists as previously reported [15,16] and used to isolate RNA and perform gene expression analyses. The FFPE pieces were taken from radical prostatectomies (patients belonging to cohort 3).…”

Section: Cohortmentioning

confidence: 99%

Clinical Utility of Ghrelin-O-Acyltransferase (GOAT) Enzyme as a Diagnostic Tool and Potential Therapeutic Target in Prostate Cancer

Jiménez‐Vacas

Gómez‐Gómez

Montero-Hidalgo

et al. 2019

JCM

Self Cite

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Recent data suggested that plasma Ghrelin O-Acyl Transferase enzyme (GOAT) levels could represent a new diagnostic biomarker for prostate cancer (PCa). In this study, we aimed to explore the diagnostic and prognostic/aggressiveness capacity of GOAT in urine, as well as to interrogate its putative pathophysiological role in PCa. We analysed urine/plasma levels of GOAT in a cohort of 993 patients. In vitro (i.e., cell-proliferation) and in vivo (tumor-growth in a xenograft-model) approaches were performed in response to the modulation of GOAT expression/activity in PCa cells. Our results demonstrate that plasma and urine GOAT levels were significantly elevated in PCa patients compared to controls. Remarkably, GOAT significantly outperformed PSA in the diagnosis of PCa and significant PCa in patients with PSA levels ranging from 3 to 10 ng/mL (the so-called PSA grey-zone). Additionally, urine GOAT levels were associated to clinical (e.g., Gleason-score, PSA levels) and molecular (e.g., CDK2/CDK6/CDKN2A expression) aggressiveness parameters. Indeed, GOAT overexpression increased, while its silencing/blockade decreased cell-proliferation in PCa cells. Moreover, xenograft tumors derived from GOAT-overexpressing PCa (DU145) cells were significantly higher than those derived from the mock-overexpressing cells. Altogether, our results demonstrate that GOAT could be used as a diagnostic and aggressiveness marker in urine and a therapeutic target in PCa.

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Spliceosome component SF3B1 as novel prognostic biomarker and therapeutic target for prostate cancer

Cited by 61 publications

References 59 publications

Roles of Splicing Factors in Hormone-Related Cancer Progression

Roles of Splicing Factors in Hormone-Related Cancer Progression

The abnormal regulation of spliceosome may be a key factor for coronary heart disease: a simple bioinformatics analysis

Clinical Utility of Ghrelin-O-Acyltransferase (GOAT) Enzyme as a Diagnostic Tool and Potential Therapeutic Target in Prostate Cancer

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