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

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.

Retracted: MicroRNA‐4429 restrains colorectal cancer cell invasion and migration via regulating SMAD3‐induced epithelial–mesenchymal transition

“…SP1‐induced LINC00511 enhances glioma progression by targeting miR‐124‐3p/CCND2 axis (Li et al, 2019). c‐MYC allows transcription and splicing of the carcinogenic splicing factor Sam68 in cancer (Caggiano et al, 2019). Thereafter, we continued to attest the modulatory mechanism underlying miR‐4429 in CRC.…”

Poison Exon Splicing Regulates a Coordinated Network of SR Protein Expression during Differentiation and Tumorigenesis

“…Few studies have investigated the molecular mechanisms driving alterations in SR protein levels, which, in tumors, frequently occurs without genomic copy number changes (Best et al, 2013;Karni et al, 2007;Park et al, 2019;Sebestyé n et al, 2016), arguing for misregulation at the post-transcriptional level. Transcriptional activation of SFs, for example by the Myc oncogene, occurs in a subset of tumors (Anczukó w et al, 2012;Caggiano et al, 2019;Das et al, 2012;David et al, 2010;Koh et al, 2015;Park et al, 2019). Therefore, investigation of the fundamental mechanisms that regulate the AS machinery is imperative.…”

LINC00667/miR-449b-5p/YY1 axis promotes cell proliferation and migration in colorectal cancer

“…Transcription factors are known as regulators of genes in nucleus [ 34 ]. Here, we predicted the potential upstream transcription factors of LINC00667 by using the online tool ALGGEN.…”