E2F5 promotes prostate cancer cell migration and invasion through regulation of TFPI2, MMP-2 and MMP-9

Karmakar, Deepmala; Maity, Jyotirindra; Mondal, Payel; Chowdhury, Puskar Shyam; Sikdar, Nilabja; Karmakar, Parimal; Das, Chandrima; Sengupta, Sanghamitra

doi:10.1093/carcin/bgaa043

Cited by 30 publications

(28 citation statements)

References 33 publications

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“…Matrix metalloproteinases are a series of important endopeptidase enzymes that degrade extracellular matrix and participate in the invasion and metastasis of many kinds of tumors. MMP-2 and MMP-9 are important members of the matrix metalloproteinases family [29]. Our results confirm that SPAG5 gene knockout promotes the expression of cleavedcaspase-3 and inhibits the expression of Ki67,VEGF, and MMP-2/-9.…”

Section: Discussionsupporting

confidence: 79%

Overexpression of sperm associated antigen 5 promotes cell growth, metastasis, and adriamycin resistance in esophageal squamous cell carcinoma via activating PI3K/AKT signaling pathway

Yan¹,

Zhang²,

Yi³

et al. 2020

Preprint

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Background: Esophageal cancer (ESCC) is one of the most common malignant tumors in the digestive system. This study aims to explore the effects of sperm associated antigen 5 (SPAG5) on cell growth, metastasis, and azithromycin resistance in esophagus cancer and its molecular mechanism.Methods: The DEGs were obtained from GSE92396, GSE17351, and GSE9982 datasets about ESCC. The PPI network was constructed using the STRING database and was visualized using Cytoscape software. The cytohubba plug-in of Cytoscape software was used to identify the hub genes of the PPI network. The DEGs were used to perform GO and KEGG pathway enrichment analysis using the DAVID database. Statistical analysis was performed to test the clinical and prognostic significance of SPAG5. Cell viability, proliferation, apoptosis, migration, and invasion were detected using CCK-8, colony formation, flow cytometry, transwell and scratch-wound assays. The expression of related genes was detected by qRT-PCR, western blot and IHC assays. The oncogenicity of SPAG5 in ESCC cells was determined using the nude mouse transplantation tumor experiment.Results: Ninety-three overlapping genes from the DEGs were used to construct the PPI network, and mainly enriched in BP, CC, and MF terms. COX regression analysis of OS showed that SPAG5 expression and pN category were correlated with OS. Univariate and multivariate analyses showed that SPAG5 was an independent prognostic factor for OS in ESCC. The ROC curve analysis showed the AUC of SPAG5 was 0.74. Multiple logistic regression showed that SPAG5 were subsequently identified as an independent risk factor associated with OS. SPAG5 overexpression was detected in ESCC tissues and cell lines, and improved cell proliferation. SPAG5 knockdown reduced cell growth and metastasis and promoted its apoptosis. The functions of SPAG5 overexpression promoting ESCC cell growth and affecting cleaved caspase-3, Ki67, VEGF, and MMP-2/-9 expression were reversed by PI3K/AKT inhibitor. SPAG5 overexpression enhanced resistance to ADM in EC9706 and Eca109 cells and it was closely related to the activation of PI3K/AKT signaling pathway.Conclusion: The overexpression of SPAG5 was an independent good prognostic factor and promoted the proliferation, invasion, migration, and ADM resistance, and inhibited the apoptosis via activating PI3K/AKT signaling pathway in ESCC.

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Section: Discussionsupporting

confidence: 79%

Overexpression of sperm associated antigen 5 promotes cell growth, metastasis, and adriamycin resistance in esophageal squamous cell carcinoma via activating PI3K/AKT signaling pathway

Yan¹,

Zhang²,

Yi³

et al. 2020

Preprint

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“…Previous studies have found that E2F5 shows higher expression in certain kinds of tumors, including PCa (49,50). Li et al reported that the up-regulation of microRNA-132 causes the down-regulation of E2F5, which may contribute to the tumorigenesis of PCa (10).…”

Section: Discussionmentioning

confidence: 98%

“…Qi et al showed that through enhancing CDK13 transcription, E2F5 leads to the up-regulation of its expression and the proliferation of PCa cells ( 49 ). Karmakar et al provided strong evidence that by regulating the level and activity of its downstream targets, E2F5 overexpression accelerates cell invasion and migration in PCa ( 50 ). In the present study, we showed that the mRNA level of E2F5 in PCa is obviously distinct from that in normal tissues.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of the functional and prognostic value of E2F transcription factors in human prostate cancer through data mining and experimental validation

Wang¹,

Tang²,

Zhang³

et al. 2021

Transl Cancer Res TCR

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Background: A growing body of evidence shows that E2F transcription factors play a significant role in the tumorigenesis of prostate cancer. However, their functional and prognostic value has not been fully illustrated. Therefore, we used bioinformatics methods to further analyze the possible roles of E2F transcription factors in the development and progression of prostate cancer. Methods:We explored the expression levels of E2F transcription factors using data from The Cancer Genome Atlas (TCGA) and Oncomine database in paired and unpaired samples. The clinical correlation and prognostic value of E2F transcription factors were assessed. Using the R package "pROC", we judged the diagnostic value of E2F transcription factors. The online website tool cBioPortal was also employed to find possible gene alterations of E2F transcription factors in samples from TCGA. The R package "clusterprofiler" was used to conduct functional analysis. Moreover, we also used the Tumor Immune Estimation Resource to search for the associations between E2F transcription factors and the infiltration levels of 6 kinds of immune cells. Finally, quantitative real-time polymerase chain reaction (PCR) was conducted to validate the expression levels of E2F transcription factors in human paired prostate tissues.Results: E2F1/2/3/5 messenger RNA (mRNA) expression levels were higher in prostate cancer tissues than in normal tissues, while E2F4 and E2F6 mRNA expression levels were lower (P<0.05). All E2F transcription factors were associated with clinical parameters. Kaplan-Meier analysis revealed that E2F1/4/6/8 were notably associated with the overall survival of patients with prostate cancer (P<0.05). Receiver operating characteristic (ROC) curve results showed that except for E2F7, the other E2F transcription factors had diagnostic value for prostate cancer (P<0.05). We further found close associations between E2F transcription factors and the infiltration levels of immune cells. The results of quantitative real-time PCR were consistent with those from public databases.Conclusions: E2F transcription factor family members are differentially expressed in prostate cancer and are significantly related to the prognosis of patients, suggesting that they may be adopted as biomarkers for prognosis prediction and the treatment of prostate cancer.

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“…EMT decreases cell-cell and cell-matrix adhesion, so as to enhance the ability of cell migration, invasion and metastasis (32). MMP-2 and MMP-9 are the most extensively investigated members of the MMP family, which can degrade the basement membrane and the extracellular matrix, and promote tumour cell migration and invasion (33)(34)(35). In the present study, it was demonstrated that miR-195-5p overexpression significantly promoted the expression of E-cadherin, and inhibited the expression of N-cadherin, vimentin and snail, while MMP-2 and MMP-9 were also suppressed, suggesting that miR-195-5p overexpression inhibited the EMT process in laryngeal cancer cells.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑195‑5p suppresses the proliferation, migration, invasion and epithelial‑mesenchymal transition of laryngeal cancer cells in vitro by targeting E2F3

et al. 2021

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Increasing evidence has indicated that microRNAs (miRNAs/miRs) play an important role in the occurrence and development of various types of cancer. The aim of the present study was to investigate the role and underlying molecular mechanisms of miR-195-5p in laryngeal cancer cell proliferation, migration and invasion. Reverse transcription-quantitative PCR (RT-qPCR) was performed to measure the expression levels of miR-195-5p in laryngeal carcinoma cell lines. The expression levels of miR-195-5p and E2F transcription factor 3 (E2F3) were modified by transfection with miR-195-5p mimics and pcDNA3.1-E2F3. A luciferase reporter assay was used to verify the association between miR-195a-5p and E2F3. Cell Counting Kit-8, cell wound healing and Transwell invasion assays were used to detect the biological functions of laryngeal cancer cells. The expression of epithelial-mesenchymal transition (EMT)-associated genes was evaluated by western blotting and RT-qPCR. The results revealed that the expression of miR-195-5p was decreased in laryngeal cancer cell lines. The overexpression of miR-195-5p inhibited the proliferation, migration, invasion and EMT of laryngeal cancer cells. Dual-luciferase reporter assays revealed that miR-195-5p could directly target E2F3 and that there was a negative association between them. E2F3 overexpression significantly attenuated the inhibitory effects of the overexpression of miR-195-5p on the proliferation, migration, invasion and EMT of laryngeal cancer cells. Collectively, the findings of the present study demonstrated that the overexpression of miR-195-5p significantly inhibited the progression of laryngeal cancer cells, and these effects may be mediated via the downregulation of the expression of E2F3.

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E2F5 promotes prostate cancer cell migration and invasion through regulation of TFPI2, MMP-2 and MMP-9

Cited by 30 publications

References 33 publications

Overexpression of sperm associated antigen 5 promotes cell growth, metastasis, and adriamycin resistance in esophageal squamous cell carcinoma via activating PI3K/AKT signaling pathway

Overexpression of sperm associated antigen 5 promotes cell growth, metastasis, and adriamycin resistance in esophageal squamous cell carcinoma via activating PI3K/AKT signaling pathway

Comprehensive analysis of the functional and prognostic value of E2F transcription factors in human prostate cancer through data mining and experimental validation

MicroRNA‑195‑5p suppresses the proliferation, migration, invasion and epithelial‑mesenchymal transition of laryngeal cancer cells in vitro by targeting E2F3

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