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DEAD-box Helicase 27 Promotes Hepatocellular Carcinoma Progression Through ERK Signaling.

ABSTRACT: Introduction: DEAD-box helicase 27 (DDX27) belongs to DEAD-Box nucleic acid helicase family. The function of DDX27 in hepatocellular carcinoma (HCC) remain enigmatic. In light of this, we tried to investigate the regulatory role and underlying mechanism of DDX27 in HCC. Materials and methods: DDX27 expression levels were detected by qRT-PCR, Western blot and immunohistochemistry assays in HCC tissues and cells. Colony formation, CCK-8, growth curve, wound healing and transwell assays were conducted to investigate the effect of DDX27 on the proliferation and metastasis of HCC cells. RNA-sequencing was performed to detect the effect of DDX27 on downstream signaling pathway. The effect of DDX27 on HCC progression was evaluated using in vivo murine xenograft model. Results: we found an increased expression of DDX27 in HCC tissues with comparison to its para-tumor tissues. The high expression levels of DDX27 were associated with poor prognosis in HCC patients. DDX27 upregulation promoted cell metastasis. Mechanistic studies suggested that DDX27 overexpression induces the major vault protein (MVP) expression and enhances the phosphorylation levels of ERK1/2. Inhibition of ERK pathway impaired the cellular metastastic abilities induced by DDX27. The induction of DDX27 in HCC progression was further confirmed from tumors in mouse model. Conclusion: our results disclose a novel mechanism by which DDX27 enhances ERK signaling during HCC progression. DDX27 might be used in targeted therapy for HCC patients.

SUBMITTER: Xiaoqian W

PROVIDER: S-EPMC8649435 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAlthough the rapid development of diagnosis and treatment has improved prognosis in early breast cancer, challenges from different therapeutic response remain due to breast cancer heterogeneity. DEAD-box helicase 27 (DDX27) had been proved to influence ribosome biogenesis and identified as a promoter in gastric and colorectal cancer associated with stem cell-like properties, while the impact of DDX27 on breast cancer prognosis and biological functions is unclear. We aimed to explore the influence of DDX27 on stem cell-like properties and prognosis in breast cancer.MethodsThe expression of DDX27 was evaluated in 24 pairs of fresh breast cancer and normal tissue by western blot. We conducted Immunohistochemical (IHC) staining in paraffin sections of 165 breast cancer patients to analyze the expression of DDX27 and its correlation to stemness biomarker. The Cancer Genome Atlas-Breast Cancer (TCGA-BRCA) database and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database were used to analyze the expression of DDX27 in breast cancer. Kaplan-Meier survival analysis were used to investigate the implication of DDX27 on breast cancer prognosis. Western blot, CCK-8 assay, Transwell assay and wound-healing assay were carried out to clarify the regulation of DDX27 on stem cell-like properties in breast cancer cells. Gene Set Enrichment Analysis (GSEA) was performed to analyze the potential molecular mechanisms of DDX27 in breast cancer.ResultsDDX27 was significantly high expressed in breast cancer compared with normal tissue. High expression of DDX27 was related to larger tumor size (p = 0.0005), positive lymph nodes (p = 0.0008), higher histological grade (p = 0.0040), higher ki-67 (p = 0.0063) and later TNM stage (p < 0.0001). Patients with high DDX27 expression turned out a worse prognosis on overall survival (OS, p = 0.0087) and disease-free survival (DFS, p = 0.0235). Overexpression of DDX27 could enhance the expression of biomarkers related to stemness and promote stem cell-like activities such as proliferation and migration in breast cancer cells.ConclusionDDX27 can enhance stem cell-like properties and cause poor prognosis in breast cancer, also may be expected to become a potential biomarker for breast cancer therapy.

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DEAD-box Helicase 27 Promotes Hepatocellular Carcinoma Progression Through ERK Signaling.

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