The E2F family as potential biomarkers and therapeutic targets in colon cancer

Yao, Huang; Lu, Fang; Shao, Yanfei

doi:10.7717/peerj.8562

Cited by 37 publications

(36 citation statements)

References 34 publications

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“…We discovered that E2F2 and E2F7 knockdown suppressed proliferation and migration abilities, promoted cell cycle arrest, and inhibited stemness of both HeLa and C-33 A cells in vitro, suggesting that E2F2 and E2F7 may function as oncogenes, leading to tumor progression or metastasis of HPV-positive and HPV-negative cervical cancer. In line with the possible role of E2Fs in human tumorigenesis, previous studies have shown overexpression of E2Fs in several human malignant tumors at both the mRNA and protein level [26][27][28][29][30][31]. Importantly, in the current study, we show evidence of an association between E2F1/2/7/8 with histological grade, lymph node metastasis, lymph vessel invasion, and deep invasion of cervical stroma.…”

Section: Discussionsupporting

confidence: 90%

“…Other studies have similarly reported an association between increased expression of E2Fs and high-risk clinicopathological factors in lung carcinoma [ 32 ], breast cancer [ 7 ], clear cell renal cell carcinoma [ 33 ], and non-muscle invasive bladder cancer [ 34 ]. In ovarian cancer, it was found that E2F1/2/5/8 are poor prognostic biomarkers and therapeutic targets [ 35 ]]; in contrast, Yao et al demonstrated that E2F1/2/3/5/7/8 are potential biomarkers for the diagnosis of colon cancer and E2F3/4/7/8 are potential targets of precision therapy [ 28 ]. In the current study, we found that genetic mutations in E2Fs are associated with poor DFS in cervical cancer, a finding that may be accounted for by Shan et al [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

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E2F1/2/7/8 as independent indicators of survival in patients with cervical squamous cell carcinoma

et al. 2020

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Background Cervical cancer is the second leading cause of death in women 20–39 years old. Because coverage for cervical cancer screening is low, and the vaccination rate of human papillomavirus (HPV) is poor in some countries, potential markers to detect the disease at early stages are needed. E2F transcription factors (E2Fs) are a family of transcription factors that function in cell proliferation, differentiation, apoptosis, and tumorigenesis. As abnormal activation and regulation of E2Fs are related to tumor development and poor prognosis, we performed bioinformatic analyses and in vitro assays to evaluate the role of E2Fs in cervical cancer. Methods Transcriptional expression of E2Fs was initially evaluated in silico using ONCOMINE and Gene Expression Profiling Interactive Analysis (GEPIA), followed by evaluation of E2F1/2/7/8 protein levels using immunohistochemistry in 88 patient tissues. E2F2 and E2F7 mRNA levels were measured by RT-qPCR. LinkedOmics and Metascape were used to predict functions of E2Fs, and in vitro experiments were performed to assess the tumorigenic role of E2F2 and E2F7. Results In silico analysis showed that E2F1/2/7/8 were significantly overexpressed in cervical cancer, findings which were confirmed at the protein level using immunohistochemistry. Further, upregulation of E2F1/2/7/8 was associated with different clinicopathological prognostic factors, including positivity for lymph vessel invasion and deep invasion of cervical stroma. Increased expression of E2F1/2/7/8 was also related to shorter overall survival (OS) and disease-free survival (DFS) in patients with cervical cancer. Using multivariate analysis, we confirmed E2F1/2/7/8 as independent prognostic factors for shorter OS of patients with cervical cancer. Finally, in vitro experiments showed that E2F2 and E2F7 are involved in cell proliferation and migration and cell cycle regulation in both HPV-positive and HPV-negative cervical cancer cells. Conclusions E2F1/2/7/8 may be prognostic biomarkers for survival of patients with cervical cancer. E2F2 and E2F7 are involved in cell proliferation, migration, and cell cycle in both HPV-positive and HPV-negative cervical cancer cells.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

E2F1/2/7/8 as independent indicators of survival in patients with cervical squamous cell carcinoma

et al. 2020

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“…Colon cancer is regarded as one of the primary reasons of mortality associated with cancers the world over ( 18 ). The E2F family is a gene group encoding a series of transcription factors in higher eukaryotes, which may participate in mammalian cell cycle regulation and DNA synthesis ( 6 ). Findings obtained from a previous study suggest that E2F1 and E2F7 have different regulatory effects on KPNA2 to promote the development of gallbladder cancer ( 19 ).…”

Section: Discussionmentioning

confidence: 99%

“…E2F transcription factor 7 (E2F7) exerts tumor suppressive role by suppressing the transcription level of genes that participated in the entry of S-phase and disease progression ( 5 ). E2F7 is among the potential targets for molecular-based treatment of colon cancer patients ( 6 ). E2F7 modulates transcription and maturation of various microRNAs (miRNAs), which could regulate gene expression post-transcriptionally, to inhibit cell proliferation ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

E2F7 Transcriptionally Inhibits MicroRNA-199b Expression to Promote USP47, Thereby Enhancing Colon Cancer Tumor Stem Cell Activity and Promoting the Occurrence of Colon Cancer

et al. 2021

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microRNAs (miRNAs) can modulate the expression level of genes in a post-transcription manner, which are closely related to growth and metastasis of colon cancer. Herein, we aimed to explore how miR-199b influences colon cancer and to characterize its underlying molecular mechanism associating with E2F transcription factor 7 (E2F7). Assays of RT-qPCR, Western blot, and immunohistochemistry were utilized to detect the expression of E2F7 in the tissue samples collected from 30 patients diagnosed with colon cancer. Flow analysis was utilized to detect the ratio of ALDH1+ and CD133+ colon cancer stem cells. The interaction between E2F7, miR-199b, USP47, and MAPK was identified by ChIP-Seq analysis, luciferase reporter, RNA pull-down, co-immunoprecipitation, as well as glutathione-S-transferase (GST) pull-down experiments. Based on the gain- and loss-of-function approaches, the cellular functions of colon cancer cells by the E2F7-regulated miR-199b/USP47/MAPK axis were assessed. It was identified that E2F7 are expressed highly in the collected colon cancer tissues. E2F7 silencing reduced the production of ALDH1+ and CD133+ colon cancer stem cells and antagonized the effects of 5-fluorouracil (5-FU) treatment. Besides, the silencing of E2F7 was observed to suppress the oxidative stress, proliferation, migration, as well as invasion of ALDH1+ cells in vitro and tumorigenesis of colon cancer cells in vivo. Our findings reveal the pro-oncogenic effect of E2F7 on colon cancer development, highlighting E2F7 as a novel target for therapeutic strategy for colon cancer.

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“…Eventually, based on the aforementioned analysis, the present study identified an intersection between the mRNAs predicted by lncRNAs and sequencing DE mRNAs. The results presented the 236 intersection mRNAs (Table SII), and certain of them have been affirmed as cancer-associated genes, for instance CDK1, CCNB1, BUB1, EGF, E2F1, E2F2, FEN1, CD36, PARP1 and EFNA1 (33,34).…”

Section: Prediction Of Mirna Binding Sites Cerna and Ppi Network Conmentioning

confidence: 84%

Long noncoding RNAs, ENST00000598996 and ENST00000524265, are correlated with favorable prognosis and act as potential tumor suppressors in bladder cancer

Shen

Wang

et al. 2020

Oncol Rep

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Bladder cancer (BC) is a serious malignancy worldwide due to its distant metastasis and high recurrence rates. Increasing evidence has indicated that dysregulated long non-coding RNAs (lncRNAs) are involved in tumorigenesis and progression in multiple malignancies. However, their clinical significances, biological functions and molecular mechanisms in BC remain poorly understood. Hence, the present study investigated the expression profile of lncRNAs and mRNAs in five BC tissues and the corresponding adjacent normal specimens using high-throughput RNA sequencing (RNA-seq). A total of 103 differentially expressed (DE) lncRNAs were identified, including 35 upregulated and 68 downregulated ones in BC tissues. Similarly, a total of 2,756 DE-mRNAs were detected, including 1,467 upregulated and 1,289 downregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, and lncRNA-miRNA-mRNA network analyses suggested that these dysregulated lncRNAs are potentially implicated in the onset and progression of BC. Subsequently, four lncRNAs (upregulated ENST00000433108; downregulated ENST00000598996, ENST00000524265 and ENST00000398461) and two mRNAs (upregulated CCNB1 and CDK1) in 64 pairs of BC and adjacent normal tissues and four BC cell lines were detected using reverse transcription-quantitative PCR and these results were consistent with the sequencing data. Additionally, Fisher's exact test, Kaplan-Meier plots, and Cox regression analyses were used for elucidating the clinical values of ENST00000598996 and ENST00000524265. Furthermore, a receiver operating characteristic curve was constructed to assess their diagnostic values. The low expression level of ENST00000598996 and ENST00000524265 was correlated with unfavorable clinicopathological parameters, and shorter progression-free and overall survival time, whereas, ENST00000433108 was not associated with either. The in vitro functional experiments also revealed that the overexpression of ENST00000598996 and ENST00000524265 decreased the proliferation, migration, and invasion abilities of BC cells. Collectively, the results of the present study provide a novel landscape of lncRNA and mRNA expression profiles in BC. In addition, the results also indicated that ENST00000598996 and ENST00000524265 may serve as tumor suppressors, potential diagnostic biomarkers and prognostic predictors for patients with BC.

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The E2F family as potential biomarkers and therapeutic targets in colon cancer

Cited by 37 publications

References 34 publications

E2F1/2/7/8 as independent indicators of survival in patients with cervical squamous cell carcinoma

E2F1/2/7/8 as independent indicators of survival in patients with cervical squamous cell carcinoma

E2F7 Transcriptionally Inhibits MicroRNA-199b Expression to Promote USP47, Thereby Enhancing Colon Cancer Tumor Stem Cell Activity and Promoting the Occurrence of Colon Cancer

Long noncoding RNAs, ENST00000598996 and ENST00000524265, are correlated with favorable prognosis and act as potential tumor suppressors in bladder cancer

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