Work

c-MYC empowers transcription and productive splicing of the oncogenic splicing factor Sam68 in cancer

Year: 2019

Type: article

Abstract: 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.

Source: Nucleic Acids Research

DOI: 10.1093/nar/gkz344

Authors: Cinzia Caggiano, Marco Pieraccioli, Valentina Panzeri, Claudio Sette, Pamela Bielli

Institutions: Fondazione Santa Lucia, Sapienza University of Rome, Università Cattolica del Sacro Cuore, University of Rome Tor Vergata

Language: English

Topic: RNA Research and Splicing

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,992