E2F7, regulated by miR‑30c, inhibits apoptosis and promotes cell cycle of prostate cancer cells

Wáng, Ying; Pei, Xiaojuan; Xu, Po; Tan, Zhibo; Zhu, Zhenwei; Guang-ping, Zhang; Jiang, Zeying; Deng, Zhiting

doi:10.3892/or.2020.7659

Cited by 21 publications

(18 citation statements)

References 46 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%

“…In addition, inhibition of E2F2 by miR-638 downregulates the proportion of CD24−/CD44 + cells and levels of SOX2 and OCT4 [30]. Regarding E2F7, Wang et al verified that inhibition of E2F7 expression in cells from prostate cancer cell lines dramatically decreased cell proliferation, increased cell cycle arrest in the G1 phase, and resulted in higher apoptotic rates compared with those in NC groups [29]. It was also found that downregulation of E2F7 by miRNA-302a/d decreased proliferation of hepatocellular carcinoma cells and significantly inhibited stemness of lung cancer stem cells by targeting the E2F7/AKT/β-catenin/ CCND1 signaling pathway [31].…”

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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“…Also, E2F7 is involved in the regulation of carcinogenic signal pathway and the progression of tumors (27,28). For example, E2F7 expression of prostate cancer tissues was found to be notably higher compared with adjacent normal tissues (27). In the present study, according to the results of luciferase reporter and western blot assay, we found that E2F7 was the target gene of miR-140-3p in LUAD cells, and E2F7 was highly expressed in LUAD tissues.…”

Section: Discussionsupporting

confidence: 56%

“…E2F Transcription Factor 7 (E2F7) was studied to play essential roles in the regulation of cell cycle progression (24)(25)(26). Also, E2F7 is involved in the regulation of carcinogenic signal pathway and the progression of tumors (27,28). For example, E2F7 expression of prostate cancer tissues was found to be notably higher compared with adjacent normal tissues (27).…”

Section: Discussionmentioning

confidence: 99%

Circ-AASDH functions as the progression of early stage lung adenocarcinoma by targeting miR-140-3p to activate E2F7 expression

Wang¹,

Wo²,

Lu³

et al. 2021

Transl Lung Cancer Res

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Background: Lung adenocarcinoma (LUAD), which is the most common subtype of non-small cell lung cancer, is a leading course of cancer-related mortality worldwide. Recently, circular RNA (CircRNAs) has become a hot spot in cancer research because of its important role in tumorigenesis and development and its superior stability. This study aims to clarify the role of circ-AASDH in LUAD and explore its competitive endogenous RNA mechanism.Methods: The circ-AASDH, miR-140-3p and E2F transcription factor 7 (E2F7) mRNA expression levels were detected via qRT-PCR. CCK-8 and colony formation assay were used to evaluate the ability of cell proliferation. Transwell assay and wound healing assay were performed to measure the invasion and migration ability. Flow cytometry was used to detect the apoptosis of cells. Moreover, Sanger sequencing, RNaseR treatment and divergent primers were used to verify the circular structure. Luciferase reporter and RNA pull-down experiment were performed to characterize the ceRNA mechanism of circ-AASDH. The xenograft model of mice was established to investigate the tumorigenicity of circ-AASDH to LUAD in vivo.Results: By screening for differentially expressed circRNAs, we found that circ-AASDH was highly expressed in LUAD tissues and cells and correlated with tumor size, clinical stage and poor prognosis.Transfection of si-circ-AASDH can inhibit the proliferation and migration of LUAD cells and promote apoptosis in vitro. In mechanism, circ-AASDH could be used as a sponge of miR-140-3p to weaken its inhibition on the expression of E2F7. Additionally, the overexpression of circ-AASDH could deduce the suppression of miR-140-3p on the malignant progression of LUAD cells. Besides, silencing of circ-AASDH inhibited cell proliferation and migration by regulating the expression of E2F7. Furthermore, overexpression of circ-AASDH can promote the growth of LUAD in vivo.Conclusions: Circ-AASDH/miR-140-3p/E2F7 regulating axis promoted the progression in LUAD. Our results provided ideas for understanding the biological mechanism of circ-AASDH and clarify potential therapeutic targets in LUAD.

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“…Among them, E2F1/2/3a are described as transcriptional activators, while E2F3b and E2F4-E2F8 are described as transcriptional repressors. Current studies have found that members of the E2F transcription factor family can affect the progression of PCa (9)(10)(11)(12). However, there are few reports on the expression of E2Fs and their prognostic significance in PCa.…”

Section: Introductionmentioning

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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E2F7, regulated by miR‑30c, inhibits apoptosis and promotes cell cycle of prostate cancer cells

Cited by 21 publications

References 46 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

Circ-AASDH functions as the progression of early stage lung adenocarcinoma by targeting miR-140-3p to activate E2F7 expression

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

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