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EIF5B increases ASAP1 expression to promote HCC proliferation and invasion.

ABSTRACT: Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide. Despite the therapeutic advances that have been achieved during the past decade, the molecular pathogenesis underlying HCC remains poorly understood. In this study, we discovered that increased expression eukaryotic translation initiation factor 5B (eIF5B) was significantly correlated with aggressive characteristics and associated with shorter recurrence-free survival (RFS) and overall survival (OS) in a large cohort. We also found that eIF5B promoted HCC cell proliferation and migration in vitro and in vivo partly through increasing ASAP1 expression. Our findings strongly suggested that eIF5B could promote HCC progression and be considered a prognostic biomarker for HCC.

SUBMITTER: Wang ZG

PROVIDER: S-EPMC5308730 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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eIF5B increases ASAP1 expression to promote HCC proliferation and invasion.

Wang Zhen-Guang ZG Zheng Hao H Gao Wei W Han Jun J Cao Jing-Zhu JZ Yang Yuan Y Li Shuai S Gao Rong R Liu Hui H Pan Ze-Ya ZY Fu Si-Yuan SY Gu Fang-Ming FM Xing Hao H Ni Jun-Sheng JS Yan Hong-Li HL Ren Hao H Zhou Wei-Ping WP

Oncotarget 20160901 38

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide. Despite the therapeutic advances that have been achieved during the past decade, the molecular pathogenesis underlying HCC remains poorly understood. In this study, we discovered that increased expression eukaryotic translation initiation factor 5B (eIF5B) was significantly correlated with aggressive characteristics and associated with shorter recurrence-free survival (RFS) and overall survival (OS) ...[more]

PMID: 27694689

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Project description:circRNAs have been demonstrated to be key regulators of bladder cancer progression. The present study aimed to investigate the effects of circular RNA (circ)_0067934 in bladder cancer progression. A total of 54 patients with primary bladder cancer were enrolled, and their tumor tissues and adjacent normal bladder tissues were collected. For in vitro functional assays, T24 cells were transfected with sicirc_0067934, and Cell Counting Kit-8 was used to analyze the proliferative capacity of T24 cells. In addition, Transwell and Matrigel assays were used to assess the cell migration and invasion abilities, and a dual-luciferase reporter assay was used to investigate the relationship between miR-1304 and circ_0067934. Finally, reverse transcription-quantitative PCR and western blotting were performed to analyze gene and protein expression levels, respectively. circ_0067934 expression levels were significantly increased in bladder cancer tissues (P<0.001), which was associated with metastasis and a significantly decreased 5-year overall (P<0.05) and disease-free survival (P<0.05). In vitro, T24 cells in the small interfering RNA (si)circ_0067934 group demonstrated significantly reduced proliferation, migration and invasion abilities compared with the si negative control (siNC) group (P<0.01). In addition, the knockdown of circ_0067934 directly increased microRNA (miR)-1304 expression levels in T24 cells. Myc was subsequently discovered to be directly inhibited by miR-1304 and circ_0067934 was observed to increase Myc expression levels in T24 cells through inhibiting miR-1304 expression levels (P<0.01). Compared with the siNC group and sicirc_0067934 + Myc overexpression group, T24 cells in the sicirc_0067934 group exhibited significantly decreased proliferative, migratory and invasive abilities (P<0.01). In conclusion, circ_0067934 was demonstrated to increase bladder cancer cell proliferation, migration and invasion through promoting Myc expression levels via the suppression of miR-1304 expression.

Project description:BackgroundHepatocellular carcinoma (HCC) is one of the most common human malignant tumors. The prognosis of HCC patients is still unsatisfying. In this study, we performed the integrated bioinformatics analysis to identify potential biomarkers and biological pathways in HCC.MethodsGene expression profiles were obtained from the Gene Expression Omnibus database (GSE55048, GSE55758, and GSE56545) for the screening of the common differentially expressed genes (DEGs) between HCC tissues and matched non-tumor tissues. DEGs were subjected to Gene Ontology, KEGG pathway, and Reactome pathway analysis. The hub genes were identified by using protein-protein interaction (PPI) network analysis. The hub genes in HCC were further subjected to overall survival analysis of HCC patients. The hub genes were further validated by in vitro functional assays.ResultsA total of 544 common differentially expressed genes were screened from three datasets. Gene Ontology, KEGG and Reactome analysis results showed that DEGs are significantly associated with the biological process of cell cycle, cell division, and DNA replication. PPI network analysis identified 20 hub genes from the DEGs. These hub genes except CENPE were all significantly up-regulated in the HCC tissues when compared to non-tumor tissues. The Kaplan-Meier survival analysis results showed that the high expression of the 20 hub genes was associated with shorter survival of the HCC patients. Further validation studies showed that knockdown of KIF14 and KIF23 both suppressed the proliferative potential, increased the caspase-3/-7 activity, up-regulated Bax expression, and promoted the invasive and migratory abilities in the HCC cells. In addition, knockdown of KIF14 and KIF23 enhanced chemosensitivity to cisplatin and sorafenib in the HCC cells. Finally, the high expression of KIF14 and KIF23 was associated with shorter progression-free survival, recurrence-free survival, and disease-specific survival of patients with HCC.ConclusionIn conclusion, the present study performed the integrated bioinformatics analysis and showed that KIF14 and KIF23 silence attenuated cell proliferation, invasion, and migration, and promoted chemosensitivity of HCC cells. KIF14 and KIF23 may serve as potential biomarkers for predicting the worse prognosis of patients with HCC.

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EIF5B increases ASAP1 expression to promote HCC proliferation and invasion.

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eIF5B increases ASAP1 expression to promote HCC proliferation and invasion.

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