c-MYC empowers transcription and productive splicing of the oncogenic splicing factor Sam68 in cancer
Open accessAbstract
The splicing factor Sam68 is upregulated in many human cancers, including prostate cancer (PCa) where it promotes cell proliferation and survival. Nevertheless, in spite of its frequent upregulation in cancer, the mechanism(s) underlying its expression are largely unknown. Herein, bioinformatics analyses identified the promoter region of the Sam68 gene (KHDRBS1) and the proto-oncogenic transcription factor c-MYC as a key regulator of Sam68 expression. Upregulation of Sam68 and c-MYC correlate in PCa patients. c-MYC directly binds to and activates the Sam68 promoter. Furthermore, c-MYC affects productive splicing of the nascent Sam68 transcript by modulating the transcriptional elongation rate within the gene. Importantly, c-MYC-dependent expression of Sam68 is under the tight control of external cues, such as androgens and/or mitogens. These findings uncover an unexpected coordination of transcription and splicing of Sam68 by c-MYC, which may represent a key step in PCa tumorigenesis.
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MYC is required for fast transcription elongation.
“Moreover, the transcription factor MYC, which directly binds to Spt5 and recruits it to promoters, allowing Spt5 transfer onto RNA Pol II (Baluapuri et al, 2019), has been shown to be required for fast transcription elongation (Liang et al, 2018; Baluapuri et al, 2019; Caggiano et al, 2019).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Caggiano et al, 2019
The Results section reports that c-MYC depletion reduced RNAPII processivity within the Sam68 gene in LNCaP cells. The Discussion says depletion reduced elongation rate at that locus, but also notes that the experiments could not completely distinguish processivity from transcription efficiency. This supports a role for c-MYC in elongation at Sam68, not the unqualified claim that MYC is required for fast transcription elongation generally. Page numbers were not supplied. (LLM, conf=0.85)
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“Moreover, the transcription factor MYC, which directly binds to Spt5 and recruits it to promoters, allowing II (Baluapuri et al , 2019), has been shown to be required for fast transcription elongation (Liang et al , 2018; Baluapuri et al , 2019; Caggiano et al , 2019).”
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Self-citation
- Authors
- Caggiano, C., Pieraccioli, M., Panzeri, V., Sette, C., & Bielli, P.
- Affiliations
- Fondazione Santa Lucia (IT)
- Università Cattolica del Sacro Cuore (IT)
- University of Rome Tor Vergata (IT)
- Corresponding author
- Sette, Claudio
- Bielli, Pamela
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-05-08
- Volume
- 47
- Issue
- 12
- Pages
- 6160-6171
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC6614821
- OpenAlex
- W2943849032
- Cited by
- 44
- References
- 52
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 7 · 2023: 6 · 2022: 11 · 2021: 6 · 2020: 7 · 2019: 1
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- PubliCatt (Università Cattolica del Sacro Cuore) (submittedVersion, cc-by-nc)
- Funders
- Italian Ministry of Health ‘Ricerca Finalizata 2011’ (GR-2011-02348423)
- Ricerca Finalizzata 2016 (RF-2016-02363460)
- AIRC (IG18790)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- Sam68, c-Myc, prostate cancer, transcriptional regulation, splicing, transcription elongation, promoter binding, androgens, mitogens, carcinogenesis
- MeSH terms
- DNA-Binding Proteins, Exons, Humans, Male, Promoter Regions, Genetic, Prostatic Neoplasms, RNA Polymerase II, Transcriptional Activation, Gene Expression Regulation, Neoplastic, Proto-Oncogene Proteins c-myc, RNA-Binding Proteins, Alternative Splicing, Heterogeneous-Nuclear Ribonucleoprotein Group F-H, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, HEK293 Cells, Transcription Elongation, Genetic
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