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Transcriptome-wide identification of transcripts regulated by PHF5A in colorectal cancer cells

ABSTRACT: Dysregulated alternative splicing (AS) plays critical roles in driving cancer progression, and the underlying mechanisms remain largely unknown. Here we demonstrated that PHF5A, a component of U2 snRNPs, was frequently upregulated in colorectal cancer (CRC) samples and associated with poor prognosis. PHF5A promoted proliferation and metastasis of CRC cells in vitro and in vivo. Transcriptomic analysis identified PHF5A-regulated AS targets and pathways. Particularly, PHF5A induced TEAD2 exon 2 inclusion to activate YAP signaling, and interference of TEAD2-L partially reversed the PHF5A-mediated tumor progression. Pharmacological inhibition of PHF5A using pladienolide B had potent antitumor activity. Collectively, these data revealed the oncogenic role of PHF5A in CRC through regulating AS, and established PHF5A as potential therapeutic target.

ORGANISM(S): Homo sapiens

PROVIDER: GSE180042 | GEO | 2021/07/16

REPOSITORIES: GEO

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Acetylation of spliceosome protein PHF5A modulates stress responses and colorectal carcinogenesis through alternative splicing mediated upregulation of KDM3A

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Splicing Modulators Act at the Branch Point Adenosine Binding Pocket Defined by the PHF5A-SF3b Complex

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