E2F2/5/8 Serve as Potential Prognostic Biomarkers and Targets for Human Ovarian Cancer

Zhou, Quan; Zhang, Fan; He, Ze; Zuo, Mingzhang

doi:10.3389/fonc.2019.00161

Cited by 66 publications

(67 citation statements)

References 53 publications

(78 reference statements)

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“…We further used ENCORI platform to nd potential target genes regulated by both miR-455-5p and miR-491-5p, and we found E2F2 as a possible target gene. The cancer-promoting role of E2F2 in ovarian cancer and other types of cancers has been well addressed [27][28][29][30]. We therefore hypothesized that LBX2-AS1 might increase the expression level of E2F2 gene in ovarian cancer cells by inhibiting miR-455-5p and miR-491-5p, and this hypothesis was veri ed by our luminescence reporter gene assay and cell functional assays.…”

Section: Discussionmentioning

confidence: 71%

LBX2-AS1 Promotes Ovarian Cancer Progression by Facilitating E2F2 Gene Expression via MIR-455-5P and MIR-491-5P Sponging

Cao

Wang

Tang

et al. 2020

Preprint

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Background:LBX2-AS1 is a long noncoding RNA that facilitates the development of gastrointestinal cancers and lung cancer, but its participation in ovarian cancer development remained uninvestigated.Methods: Clinical data retrieved from TCGA ovarian cancer database and the clinography of 60 ovarian cancer patients who received anti-cancer treatment in our facility were analyzed. The overall cell growth, colony formation, migration, invasion, apoptosis and tumor formation on nude mice of ovarian cancer cells were evaluated before and after lentiviral-based LBX2-AS1 knockdown. ENCORI platform was used to explore LBX2-AS1-interacting microRNAs and target genes of the candidate microRNAs. Luciferase reporter gene assay and RNA-pulldown assay were used to verify the putative miRNA-RNA interactions.Results: Ovarian cancer tissue specimens showed significant higher LBX2-AS1 expression levels that non-cancerous counterparts. High expression level of LBX2-AS1 significantly associated with patients reduced overall survival. LBX2-AS1 knockdown significantly downregulated the cell growth, colony formation, migration, invasion and tumor formation capacity of ovarian cancer cells and increased their apoptosis in vitro. LBX2-AS1 interacts with and thus inhibits the function of miR-455-5p and miR-491-5p, both of which restrained the expression of E2F2 gene in ovarian cancer cells via mRNA targeting. Transfection of miRNA inhibitors of these two miRNAs or forced expression of E2F2 counteracted the effect of LBX2-AS1 knockdown on ovarian cancer cells.ConclusionsLBX2-AS1 was a novel cancer-promoting lncRNA in ovarian cancer. This lncRNA increased the cell growth, survival, migration, invasion and tumor formation of ovarian cancer cells by inhibiting miR-455-5p and miR-491-5p, thus liberating the expression of E2F2 cancer-promoting gene.

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Section: Discussionmentioning

confidence: 71%

LBX2-AS1 Promotes Ovarian Cancer Progression by Facilitating E2F2 Gene Expression via MIR-455-5P and MIR-491-5P Sponging

Cao

Wang

Tang

et al. 2020

Preprint

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“…Quan Zhou et al. reported that overexpressed E2F2 is closely related to poor post progression survival in ovarian cancer patients, and can be used for targeted treatment and prognosis prediction [5]. Similar results can be found in glioma [6] osteosarcoma [7], gastric cancer [8] and melanoma [9], it's not surprising that E2F2 is regarded as oncogene.…”

Section: Introductionmentioning

confidence: 74%

Increased E2F2 predicts poor prognosis in patients with HCC based on TCGA data

Zeng

Cao

Tang³

2020

Preprint

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Background: The E2F family of transcription factor 2 (E2F2) plays an important role in the development and progression of various tumors, but its association with hepatocellular carcinoma remains unknown. The aim of our study was to investigate the role and clinical significance of E2F2 in hepatocellular carcinoma (HCC).Methods: HCC raw data were extracted from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test, Kruskal-Wallis test and logistic regression was applied to analyze the relationship between the expression of E2F2 and clinicopathologic characteristics. Cox regression and Kaplan-Meier was employed to evaluate the correlation between clinicopathologic features and survival. The biological function of E2F2 was annotated by Gene set enrichment analysis (GSEA).Results: The expression of E2F2 was increased in HCC samples. The expression of elevated E2F2 in HCC samples was prominently correlated with histologic grade (OR =2.62 for G3-4 vs. G1-2, p=1.80E-05), clinical stage (OR =1.74 for III-IV vs. I-II, p=0.03), T (OR =1.64 for T3-4 vs.T1-2, p=0.04), tumor status (OR =1.88 for with tumor vs. tumor free, p= 3.79E-03), plasma alpha fetoprotein (AFP) value (OR =3.18 for AFP≥400 vs AFP＜20, p= 2.16E-04; OR=2.50 for 20≤AFP＜400 vs AFP＜20, p=2.56E-03). Increased E2F2 had an unfavorable OS (p=7.468e−05), PFI (p=3.183e−05), DFI (p=0.001), DSS (p=4.172e−05). Elevated E2F2 was independently bound up with OS (p =0.004 , hazard ratio [HR]= 2.4 (95% CI [1.3-4.2])), DFI (P =0.029, hazard ratio [HR] = 2.0 (95% CI [1.1-3.7])) and PFI (P =0.005, hazard ratio [HR] = 2.2 (95% CI [1.3-3.9])) . GSEA disclosed that cell circle, RNA degradation, pyrimidine metabolism, base excision repair, aminoacyl tRNA biosynthesis, DNA replication, p53 signaling pathway, nucleotide excision repair, ubiquitin mediated proteolysis, citrate cycle TCA cycle were notably enriched in E2F2 high expression phenotype.Conclusions: Elevated E2F2 can be a promising independent prognostic biomarker and therapeutic target for HCC. Additionally, cell cycle, pyrimidine metabolism, DNA replication, p53 signaling pathway, ubiquitin mediated proteolysis, the citrate cycle TCA cycle may be the key pathway by which E2F2 participate in the initial and progression of HCC.

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“…As transcription factors that regulate the cell cycle, E2F family members are involved in the development of various cancers (12). Although the role of E2Fs in tumorigenesis and their prognostic value have been con rmed (6)(7)(8)(9), it is still necessary to clarify the different roles of E2F family members in gastric cancer. In this study, we analyzed the expression, mutation and prognostic value of different E2F family members in gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

“…The main functions of E2F proteins are to regulate the cell cycle, cell differentiation, the DNA damage response and cell death (4). E2F proteins have been found in several human malignant tumors, including breast cancer (5), ovarian cancer (6), bladder cancer (7), prostate cancer (8), lung cancer (9) and gastrointestinal cancer (10).…”

Section: Introductionmentioning

confidence: 99%

The roles of E2Fs in gastric cancer: the transcription factors E2F1/2/3/4/5 as potential therapeutic targets and E2F6/7/8 as new prognostic biomarkers in gastric cancer

Li¹,

Zhao²,

Shen³

et al. 2020

Preprint

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Background E2F is a family of transcription factor proteins with multiple functions; E2F proteins are involved in cell cycle regulation, cell differentiation, the DNA damage response and cell death. Studies have shown that E2Fs have prognostic significance in many cancers, but the expression patterns and prognostic values of E2Fs in gastric cancer have not been systematically elucidated. Methods In this study, we used the ONCOMINE database and UALCAN online analysis website to compare the transcriptional levels and expression of eight E2F family members between gastric cancer and normal samples. UALCAN was also used to analyze the relationship between the expression of 8 E2F members and clinicopathological parameters. The prognostic value of the E2Fs were determined by Kaplan-Meier Plotter. A protein-protein interaction (PPI) network was constructed using the STRING database. The functions and pathways of E2F family and its neighboring 50 frequently changed genes were analyzed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) software. Finally, quantitative PCR was used to verify the expression of E2Fs in gastric cancer cells. Results The expression patterns of 8 E2F members were significantly related to the clinical cancer stage and tumor grade of gastric cancer patients. High mRNA expression of E2F1/2/3/4/5 was a prognostic factor for poor OS in gastric cancer patients, while high expression of E2F6/7/8 was associated with better OS. In addition, a high mutation rate (46%) for E2Fs was observed in patients with gastric cancer. The expression levels of E2F1/2/3/5/8 in AGS and HGC27 cell lines were higher than those in normal cells, while E2F7 showed the opposite trend. Conclusions In summary, these results indicate that E2F1/2/3/4/5 can be used as potential therapeutic targets in gastric cancer, and E2F6/7/8 can be used as new prognostic markers to improve the survival rate and prognostic accuracy in gastric cancer.

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E2F2/5/8 Serve as Potential Prognostic Biomarkers and Targets for Human Ovarian Cancer

Cited by 66 publications

References 53 publications

LBX2-AS1 Promotes Ovarian Cancer Progression by Facilitating E2F2 Gene Expression via MIR-455-5P and MIR-491-5P Sponging

LBX2-AS1 Promotes Ovarian Cancer Progression by Facilitating E2F2 Gene Expression via MIR-455-5P and MIR-491-5P Sponging

Increased E2F2 predicts poor prognosis in patients with HCC based on TCGA data

The roles of E2Fs in gastric cancer: the transcription factors E2F1/2/3/4/5 as potential therapeutic targets and E2F6/7/8 as new prognostic biomarkers in gastric cancer

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