Derlin-1 Promotes the Progression of Human Hepatocellular Carcinoma via the Activation of AKT Pathway.

INTRODUCTION

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. In the present research, we explored a new oncogene, derlin-1 (DERL1), and studied its role and mechanism in human HCC.

METHODS

We assessed the expression and prognosis value of DERL1 in human HCC by using GEPIA dataset analysis and immunohistochemistry. To elucidate the specific function of DERL1, we suppressed its expression in two HCC cell lines, HuH7 and Hep3B, and overexpressed DERL1 in Hep3B cells. Cell proliferation and migration was detected by CCK8 and transwell assays. Cell flow cytometry was used to evaluate cell apoptosis.

RESULTS

Our results demonstrated that DERL1 was highly expressed in HCC samples (n = 369) than in normal samples (n = 160). Similar results were obtained in 60 clinical samples that we collected from the local hospital. The high expression rate of DERL1 reached 78.3% (47/60). DERL1 overexpression samples were concentrated in patients with tumor diameters >5cm or lymph node metastases. Thus, we speculated that DERL1 operated as a tumor promotor in HCC, and its expression might be proposed as a predictor for tumor metastasis of human HCC. Interference of DERL1 markedly blocked cell proliferation and migration, and induced the apoptosis of HCC cells in vitro. Phosphorylation of Akt was significantly inhibited in cells transfected with DERL1 siRNA compared to their control cells in HuH7 and Hep3B cell lines. The opposite result was observed in the DERL1 overexpression cells.

CONCLUSION

Our findings prove that DERL1 promotes tumor progression via AKT pathway and provide a new potential target for the clinical treatment and diagnosis of human HCC.