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PRPF4B drives hepatocellular carcinoma progression by modulating NF-κB signaling via TIA1-regulated alternative

Canxue Zhang1, Zhihong Huang1, Yuting Su1

  • 1State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Cellular Signalling
|April 3, 2026
PubMed

Insights

PRPF4B promotes hepatocellular carcinoma (HCC) growth and sorafenib resistance. Inhibiting PRPF4B induces DNA damage, halts cell cycle, and enhances sorafenib sensitivity by blocking the NF-κB pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Splicing kinase family members, including PRPF4B, are implicated in tumor progression.
  • The specific role of PRPF4B in hepatocellular carcinoma (HCC) remains largely undefined.
  • Understanding PRPF4B's mechanisms in HCC is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the role and underlying mechanisms of PRPF4B in hepatocellular carcinoma (HCC).
  • To determine if PRPF4B expression correlates with patient prognosis and sorafenib response.
  • To explore PRPF4B as a potential therapeutic target for HCC.

Main Methods:

  • PRPF4B expression analysis in HCC patient data.
  • In vitro knockdown of PRPF4B in HCC cell lines.
  • Assessment of cell proliferation, migration, invasion, and apoptosis.
  • Analysis of DNA damage, cell cycle progression, and key protein markers (e.g., γ-H2AX, CDC2, CDC25C, cyclin B1).
  • Investigation of the NF-κB pathway and PRPF4B interaction with TIA1.

Main Results:

  • PRPF4B expression is upregulated in HCC and associated with poor prognosis.
  • PRPF4B knockdown suppresses HCC cell proliferation, migration, invasion, and induces apoptosis.
  • PRPF4B knockdown leads to ROS accumulation, DNA damage, and G2/M cell cycle arrest.
  • PRPF4B is upregulated in sorafenib non-responders; its knockdown sensitizes HCC cells to sorafenib.
  • PRPF4B knockdown inhibits HCC proliferation via the NF-κB pathway and alters TIA1 splicing.

Conclusions:

  • PRPF4B plays a significant oncogenic role in HCC by promoting proliferation and invasion.
  • PRPF4B knockdown induces anti-tumor effects through DNA damage and cell cycle arrest.
  • PRPF4B is linked to sorafenib resistance, and its inhibition can enhance treatment efficacy.
  • PRPF4B interacts with TIA1, modulating splicing and inhibiting the NF-κB pathway, making it a potential therapeutic target.
Keywords:
Alternative splicingHepatocellular carcinomaNF-κBPRPF4BSorafenib

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