Abstract
Background: Hepatocellular carcinoma (HCC) is one of the major causes of tumor-related morbidity and mortality worldwide. Accumulating evidence has revealed that aberrant expression of crucial cancer-related genes contributes to hepatocellular carcinogenesis. This study aimed to characterize the biological role of DEP domain containing 1 (DEPDC1), a novel cancer-related gene, in HCC and illuminate the potential molecular mechanisms involved.Materials and methods: Quantitative real-time PCR (qRT-PCR), Western blotting and immunohistochemical (IHC) staining were used to characterize the expression patterns of DEPDC1 in tumorous tissues and adjacent normal tissues. Kaplan–Meier survival analysis was launched to evaluate the relationship between DEPDC1 expression and overall survival. CCK8 assay, colony formation and flow cytometry were performed to investigate the effects of DEPDC1 on HCC cell viability, clonogenic capability and cell apoptosis. Murine xenograft models were established to determine the effect of DEPDC1 on tumor growth in vivo. SP600125, a JNK specific inhibitor, was applied to carriy out mechanistic studies.Results: DEPDC1 was significantly up-regulated in HCC tissues compared with para-cancerous tissues. Besides, patients with high DEPDC1 expression experienced a significantly shorter overall survival. Functional investigations demonstrated that DEPDC1 overexpression facilitated HCC cell proliferation and suppressed cell apoptosis, whereas DEPDC1 depletion inhibited cell proliferation and promoted cell apoptosis. Furthermore, DEPDC1 ablation suppressed tumorigenecity of HCC cells in murine xenograft models. Mechanistic studies uncovered that JNK signaling pathway mediated the promoting effects of DEPDC1 on HCC cell viability and chemotherapy resistance.Conclusion: Collectively, our data may provide some evidence for DEPDC1 as a candidate therapeutic target for HCC.
Highlights
Hepatocellular carcinoma (HCC) is one of the major causes of tumor-related morbidity and mortality worldwide
We found that DEP domain containing 1 (DEPDC1) was significantly up-regulated in HCC tissues compared with adjacent normal tissues
To assess the relationship between DEPDC1 expression and overall survival of HCC patients, tumorous tissues were classified into high DEPDC1 expression group and low DEPDC1 expression group based on the average value of its mRNA expression levels
Summary
Hepatocellular carcinoma (HCC) is one of the major causes of tumor-related morbidity and mortality worldwide. Mechanistic studies uncovered that JNK signaling pathway mediated the promoting effects of DEPDC1 on HCC cell viability and chemotherapy resistance. Hepatocellular carcinoma, one of the most prevalent human malignancies, ranks the third most leading cause of tumor-related mortality worldwide, with approximately 600,000 deaths occurring annually [1,2,3]. It is estimated by American Cancer Research Society that more than 40,000 HCC cases were newly diagnosed and approximately 28,000 patients died of this cancer in the United States in 2017 [4].
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