MARK1 suppress malignant progression of hepatocellular carcinoma and improves sorafenib resistance through negatively regulating POTEE.

Abstract

Purpose: This study aimed to investigate the role of microtubule-affinity regulatory protein kinase 1 (MARK1) in hepatocellular carcinoma (HCC) progression, its association with sorafenib sensitivity, and the interplay between MARK1 and POTE Ankyrin domain family member E(POTEE) in HCC cells.

Methods: Quantitative real-time polymerase chain reaction analysis was used to assess MARK1 and POTEE expression in 60 pairs of HCC tissues and cell lines. The correlation between MARK1 levels, clinicopathological features, and patient prognosis was analyzed. Sorafenib-resistant HCC cell models were developed, followed by MARK1 overexpression to evaluate its impact on cell functions. Luciferase reporter assays and rescue experiments were conducted to elucidate the MARK1-POTEE regulatory mechanism.

Results: MARK1 exhibited decreased mRNA expression in HCC tissues and cells, correlating with adverse clinicopathological features and poorer patient survival. Luciferase assays confirmed direct binding between MARK1 and POTEE. Sorafenib treatment increased MARK1 protein levels, reduced POTEE, and inhibited cell proliferation. Overexpressing MARK1 suppressed sorafenib-induced proliferation in resistant cells, while co-overexpression of MARK1 and POTEE reversed this effect.

Conclusion: MARK1 potentially restrains HCC progression and enhances sorafenib resistance by negatively modulating POTEE expression, highlighting its significance as a therapeutic target in HCC treatment.