Dataset Information

High eukaryotic initiation factor 5A2 expression predicts poor prognosis and may participate in the SNHG16/miR-10b-5p/EIF5A2 regulatory axis in head and neck squamous cell carcinoma.

ABSTRACT:

Background

This study attempted to investigate the significance of eukaryotic initiation factor 5A2 (EIF5A2) in the prognosis and regulatory network of head and neck squamous cell carcinoma (HNSCC).

Methods

EIF5A2 expression, prognostic information, and methylation levels of HNSCC were collected from the Cancer Genome Atlas (TCGA) database. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot analyses were performed to determine EIF5A2 levels in HNSCC and normal tissue samples. R software was employed for expression analysis and prognosis assessment of EIF5A2 in HNSCC. A competing endogenous RNA (ceRNA) network was generated with the starBase database. Gene set enrichment analysis (GSEA) was used to determine the enriched physiological functions and network related to high expression of EIF5A2 in HNSCC. Immune infiltration-related outcomes were acquired from the CIBERSORT and Tumor Immune Estimation Resource (TIMER) database.

Results

EIF5A2 overexpression was observed in HNSCC and linked to poor progression-free survival and overall survival time. Cox regression analyses showed that EIF5A2 level was a stand-alone indicator of HNSCC patients' prognosis. A ceRNA network analysis highlighted the SNHG16/miR-10b-5p/EIF5A2 axis in EIF5A2 regulation. The GSEA results indicated that EIF5A2 was involved in complex signaling pathways. The CIBERSORT and TIMER databases revealed significant associations between EIF5A2 expression and immune cell infiltration.

Conclusion

EIF5A2 overexpression may be a risk factor for prognosis in HNSCC and may be regulated by the SNHG16/miR-10b-5p/EIF5A2 axis.

SUBMITTER: Ye S

PROVIDER: S-EPMC9833988 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

High eukaryotic initiation factor 5A2 expression predicts poor prognosis and may participate in the SNHG16/miR-10b-5p/EIF5A2 regulatory axis in head and neck squamous cell carcinoma.

Ye Shuang S Wang Dan D Jin Ming M Du Juan J Chen Xue X Zhang Hui H Zhou Chongchang C Fang Shuai S Liu Kaitai K

Journal of clinical laboratory analysis 20221222 1

<h4>Background</h4>This study attempted to investigate the significance of eukaryotic initiation factor 5A2 (EIF5A2) in the prognosis and regulatory network of head and neck squamous cell carcinoma (HNSCC).<h4>Methods</h4>EIF5A2 expression, prognostic information, and methylation levels of HNSCC were collected from the Cancer Genome Atlas (TCGA) database. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot analyses were performed to determine EIF5A2 ...[more]

PMID: 36550070

Similar Datasets

Project description:Eukaryotic translation initiation factor 5A2 (EIF5A2) plays an important role in tumor progression and prognosis evaluation. However, little information is available about its potential role in gastric cancer. This study aimed to investigate the function of EIF5A2 in tumor progression and its potential mechanisms. EIF5A2 expression was measured in human gastric cancer cell lines, the immortalized gastric mucosal epithelial cell line (GES-1) and human gastric cancer tissues and knocked down by RNA interference or upregulated by EIF5A2 plasmid transfection. Cell proliferation, migration and invasion were assessed in vitro. The downstream targets of EIF5A2 were examined by western blotting. EIF5A2 and its potential target metastasis-associated protein 1 (MTA1) expression were examined in 160 pairs of human gastric cancer and adjacent non-tumor specimens using immunohistochemistry (IHC) staining, and its correlation with clinicopathological features and survival was investigated. Knockdown of EIF5A2 or MTA1 caused an apparent suppression of HGC27 cell proliferation, migration and invasion. After knockdown of EIF5A2 in HGC27 cells, E-cadherin levels were upregulated and vimentin, cyclin D1, cyclin D3, C-MYC and MTA1 levels were downregulated. Upregulation of EIF5A2 in MKN45 cells resulted in the converse. IHC results showed a positive correlation between EIF5A2 and MTA1 expression in gastric cancers (P<0.001). Both EIF5A2 and MTA1 overexpression were correlated with pT stage (P=0.018 and P=0.042), pN stage (P=0.037 and P=0.020) and lymphovascular invasion (P=0.016 and P=0.044). EIF5A2 or MTA1 overexpression was significantly associated with poor overall survival and disease-free survival (All P<0.05). Multivariate analyses identified EIF5A2 as an independent predictor for both overall survival (P=0.012) and disease-free survival (P=0.008) in gastric cancer patients. Our findings indicate that EIF5A2 upregulation plays an important oncogenic role in gastric cancer. EIF5A2 may represent a new predictor for poor survival and is a potential therapeutic target for gastric cancer.

Project description:BackgroundEukaryotic Initiation Factor 5A (eIF-5A), an essential translation factor, is post-translationally activated by the polyamine spermidine. Two human genes encode eIF-5A, being eIF5-A1 constitutively expressed whereas eIF5-A2 is frequently found overexpressed in human tumours. The contribution of both isoforms with regard to cellular proliferation and invasion in non-small cell lung cancer remains to be characterized.MethodsWe have evaluated the use of eIF-5A2 gene as prognosis marker in lung adenocarcinoma (LUAD) patients and validated in immunocompromised mice. We have used cell migration and cell proliferation assays in LUAD lines after silencing each eIF-5A isoform to monitor their contribution to both phenotypes. Cytoskeleton alterations were analysed in the same cells by rhodamine-phalloidin staining and fluorescence microscopy. Polysome profiles were used to monitor the effect of eIF-5A2 overexpression on translation. Western blotting was used to study the levels of eIF-5A2 client proteins involved in migration upon TGFB1 stimulation. Finally, we have co-localized eIF-5A2 with puromycin to visualize the subcellular pattern of actively translating ribosomes.ResultsWe describe the differential functions of both eIF-5A isoforms, to show that eIF5-A2 properties on cell proliferation and migration are coincident with its features as a poor prognosis marker. Silencing of eIF-5A2 leads to more dramatic consequences of cellular proliferation and migration compared to eIF-5A1. Overexpression of eIF-5A2 leads to enhanced global translation. We also show that TGFβ signalling enhances the expression and activity of eIF-5A2 which promotes the translation of polyproline rich proteins involved in cytoskeleton and motility features as it is the case of Fibronectin, SNAI1, Ezrin and FHOD1. With the use of puromycin labelling we have co-localized active ribosomes with eIF-5A2 not only in cytosol but also in areas of cellular protrusion. We have shown the bulk invasive capacity of cells overexpressing eIF-5A2 in mice.ConclusionsWe propose the existence of a coordinated temporal and positional interaction between TFGB and eIF-5A2 pathways to promote cell migration in NSCLC. We suggest that the co-localization of actively translating ribosomes with hypusinated eIF-5A2 facilitates the translation of key proteins not only in the cytosol but also in areas of cellular protrusion. Video Abstract.

Project description:Cervical carcinoma is one of the leading causes of cancer-related death for female worldwide. Eukaryotic initiation factor 5A2 belongs to the eukaryotic initiation factor 5A family and is proposed to be a key factor involved in the development of diverse cancers. In the current study, a series of in vivo and in vitro investigations were performed to characterize the role of eukaryotic initiation factor 5A2 in oncogenesis and metastasis of cervical carcinoma. The expression status of eukaryotic initiation factor 5A2 in 15 cervical carcinoma patients was quantified. Then, the effect of eukaryotic initiation factor 5A2 knockdown on in vivo tumorigenicity ability, cell proliferation, cell cycle distribution, and cell mobility of HeLa cells was measured. To uncover the mechanism driving the function of eukaryotic initiation factor 5A2 in cervical carcinoma, expression of members within RhoA/ROCK pathway was detected, and the results were further verified with an RhoA overexpression modification. The level of eukaryotic initiation factor 5A2 in cervical carcinoma samples was significantly higher than that in paired paratumor tissues ( P < .05). And the in vivo tumorigenic ability of HeLa cells was reduced by inhibition of eukaryotic initiation factor 5A2. Knockdown of eukaryotic initiation factor 5A2 in HeLa cells decreased the cell viability compared with normal cells and induced G1 phase cell cycle arrest ( P < .05). Moreover, the cell migration ability of eukaryotic initiation factor 5A2 knockdown cells was dramatically inhibited. Associated with alterations in phenotypes, RhoA, ROCK I, and ROCK II were downregulated. The above-mentioned changes in eukaryotic initiation factor 5A2 knockdown cells were alleviated by the overexpression of RhoA. The major findings outlined in the current study confirmed the potential of eukaryotic initiation factor 5A2 as a promising prognosis predictor and therapeutic target for cervical carcinoma treatment. Also, our data inferred that eukaryotic initiation factor 5A2 might function in carcinogenesis of cervical carcinoma through an RhoA/ROCK-dependent manner.

Project description:Hepatocellular carcinoma (HCC) is an invasive malignant neoplasm with a poor prognosis. The development of chemoresistance severely obstructs the chemotherapeutic efficiency of HCC treatment. Therefore, understanding the mechanisms of chemoresistance is important for improving the outcomes of patients with HCC. Eukaryotic translation initiation factor 5A2 (eIF5A2), which is considered to be an oncogene, has been reported to mediate chemoresistance in various types of cancer; however, its precise role in HCC remains unclear. Accumulating evidence has suggested that autophagy serves a dual role in cancer chemotherapy. The present study aimed to investigate the role of autophagy in eIF5A2‑mediated doxorubicin resistance in HCC. High expression levels of eIF5A2 in human HCC tissues were observed by immunohistochemistry using a tissue microarray, which was consistent with the results of reverse transcription‑quantitative PCR analysis in paired HCC and adjacent healthy tissues. HCC patient‑derived tumor xenograft mouse model was used for the in vivo study, and knockdown of eIF5A2 effectively enhanced the efficacy of doxorubicin chemotherapy compared with that in the control group. Notably, eIF5A2 served as a repressor in regulating autophagy under chemotherapy. Silencing of eIF5A2 induced doxorubicin sensitivity in HCC cells by triggering lethal autophagy. In addition, 5‑ethynyl‑2'‑deoxyuridine, lactate dehydrogenase release assay and calcein‑AM/PI staining were used to determine the enhanced autophagic cell death induced by the silencing of eIF5A2 under doxorubicin treatment. Suppression of autophagy attenuated the sensitivity of HCC cells to doxorubicin induced by eIF5A2 silencing. The results also demonstrated that knockdown of the Beclin 1 gene, which is an autophagy regulator, reversed the enhanced autophagic cell death and doxorubicin sensitivity induced by eIF5A2 silencing. Taken together, these results suggested eIF5A2 may mediate the chemoresistance of HCC cells by suppressing autophagic cell death under chemotherapy through a Beclin 1‑dependent pathway, and that eIF5A2 may be a novel potential therapeutic target for HCC treatment.

Dataset Information

High eukaryotic initiation factor 5A2 expression predicts poor prognosis and may participate in the SNHG16/miR-10b-5p/EIF5A2 regulatory axis in head and neck squamous cell carcinoma.

Background

Methods

Results

Conclusion

Publications

High eukaryotic initiation factor 5A2 expression predicts poor prognosis and may participate in the SNHG16/miR-10b-5p/EIF5A2 regulatory axis in head and neck squamous cell carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets