SRPK Inhibitors Reduce the Phosphorylation and Translocation of SR Protein Splicing Factors, thereby Correcting BIN1, MCL-1 and BCL2 Splicing Errors and Enabling Apoptosis of Cholangiocarcinoma Cells

        Cholangiocarcinoma (CCA), a common bile duct cancer in Thailand, has poor survival rates due to limited diagnostic and treatment options. mRNA splicing errors, driven by overactive splicing factors (SRSFs) activated by SRPK enzymes, are linked to CCA development. Data from The Cancer Genome Atlas (TCGA) was analyzed to study the relationship between SRPK expression and patient survival. The effects of two SRPK inhibitors, SRPIN340 and SPHINX31, were tested on CCA cells. High SRPK1 and SRPK2 levels, particularly SRPK1, were associated with shorter survival. SRPIN340 and SPHINX31 increased cancer cell death and disrupted the nuclear movement of SRSFs. This reduced splicing errors, leading to a decrease in anti-apoptotic BIN1 and an increase in pro-apoptotic MCL-1 and BCL2 variants. SRPK inhibitors, SRPIN340 and SPHINX31, show potential as treatments for CCA by correcting splicing errors and promoting cancer cell death.

Reference

Changphasuk P, Inpad C, Horpaopan S, Khunchai S, Phimsen S, Surangkul D, Janvilisri T, Silsirivanit A, Kaewkong W. SRPK Inhibitors Reduce the Phosphorylation and Translocation of SR Protein Splicing Factors, thereby Correcting BIN1, MCL-1 and BCL2 Splicing Errors and Enabling Apoptosis of Cholangiocarcinoma Cells. Front. Biosci. (Schol Ed) 2024; 16(3): 17.

DOI: 10.31083/j.fbs1603017