Elevated FAM134B expression induces radiation-sensitive in hepatocellular carcinoma

Area of Science:

• Oncology
• Molecular Biology
• Radiotherapy Research

Background:

• Family with sequence similarity 134 member B (FAM134B) role in malignancy is known, but its function in Hepatocellular Carcinoma (HCC) radiotherapy resistance is unclear.
• Clarifying FAM134B's mechanism in HCC could identify biomarkers to overcome treatment resistance.

Purpose of the Study:

• To investigate the role and molecular mechanism of FAM134B in HCC radiotherapy resistance.
• To determine if FAM134B can serve as a biomarker for predicting or overcoming radiotherapy resistance in HCC.

Main Methods:

• Real-time PCR and Western blot to assess FAM134B expression.
• Immunohistochemistry (IHC) to correlate FAM134B with patient characteristics.
• In vitro and in vivo functional assays (e.g., cell viability, apoptosis) to evaluate FAM134B's oncogenic role.
• Luciferase assays to elucidate the molecular mechanism involving JAK/Stat3 signaling.

Main Results:

• FAM134B was found to be downregulated in HCC and correlated with increased radiation resistance.
• Overexpression of FAM134B sensitized HCC cells to radiation, while inhibition led to resistance.
• FAM134B interacts with FLT3, and its downregulation activates the JAK/Stat3 pathway.
• Inhibiting JAK/Stat3 counteracted FAM134B downregulation-induced resistance and improved therapeutic efficacy.

Conclusions:

• FAM134B downregulation promotes HCC radioresistance via the JAK/Stat3 pathway.
• FAM134B represents a potential therapeutic biomarker for enhancing radiotherapy in HCC patients.