E2F8 regulates the proliferation and invasion through epithelial-mesenchymal transition in cervical cancer

Kim, Lee Kyung; Park, Sun-Ae; Eoh, Kyung Jin; Heo, Tae‐Hwe; Kim, Young Tae; Kim, Hee Jung

doi:10.7150/ijbs.37686

Cited by 25 publications

(18 citation statements)

References 26 publications

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“…Similarly, to what we observed in Msi1 knockdown or KO cells [ 3 ], inhibition of E2F2 expression arrests cell division in the G1 phase [ 94 ]. E2F8 is still poorly characterized in the context of brain tumors but it has been implicated in the development of various cancer types including lung cancer, lymphoma, colon cancer, cholangiocarcinoma, prostate cancer, hepatocellular carcinoma and breast cancer [ 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 ]. E2F8 high expression is strongly associated with a worse outcome of GBM patients and radio-resistance while E2F8 knockdown decreased proliferation and tumor growth and inhibited invasion, migration and the expression of genes implicated in metastasis [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Musashi1 Contribution to Glioblastoma Development via Regulation of a Network of DNA Replication, Cell Cycle and Division Genes

Baroni

Choudhary

et al. 2021

Cancers

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RNA-binding proteins (RBPs) function as master regulators of gene expression. Alterations in their levels are often observed in tumors with numerous oncogenic RBPs identified in recent years. Musashi1 (Msi1) is an RBP and stem cell gene that controls the balance between self-renewal and differentiation. High Msi1 levels have been observed in multiple tumors including glioblastoma and are often associated with poor patient outcomes and tumor growth. A comprehensive genomic analysis identified a network of cell cycle/division and DNA replication genes and established these processes as Msi1’s core regulatory functions in glioblastoma. Msi1 controls this gene network via two mechanisms: direct interaction and indirect regulation mediated by the transcription factors E2F2 and E2F8. Moreover, glioblastoma lines with Msi1 knockout (KO) displayed increased sensitivity to cell cycle and DNA replication inhibitors. Our results suggest that a drug combination strategy (Msi1 + cell cycle/DNA replication inhibitors) could be a viable route to treat glioblastoma.

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Section: Discussionmentioning

confidence: 99%

Musashi1 Contribution to Glioblastoma Development via Regulation of a Network of DNA Replication, Cell Cycle and Division Genes

Baroni

Choudhary

et al. 2021

Cancers

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“…Recent reports showed that E2F1 promotes EMT by regulating ZEB2 in small lung cancer [19]. Our previous research showed that E2F8 was also involved in invasion and metastasis by EMT in cervical cancer [20]. These results showed that E2F8 is closely associated with EMT, but the detailed mechanism of EMT regulation by E2F8 in ovarian cancer is unknown.…”

Section: Introductionmentioning

confidence: 91%

E2F8 Induces Cell Proliferation and Invasion through the Epithelial–Mesenchymal Transition and Notch Signaling Pathways in Ovarian Cancer

Eoh

Kim

Lee

et al. 2020

IJMS

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Background: Despite the recent research implicating E2F8 (E2F Transcription Factor 8) in cancer, the role of E2F8 in the progression of ovarian cancer has remained unclear. Hence, we explored the bio-functional effects of E2F8 knockdown on ovarian cancer cell lines in vitro and in vivo. Methods: The expression of E2F8 was compared between ovarian cancer and noncancer tissues, and its association with the progression-free survival of ovarian cancer patients was analyzed. To demonstrate the function of E2F8 in cell proliferation, migration, and invasion, we employed RNA interference to suppress E2F8 expression in ovarian cancer cell lines. Finally, the effect of E2F8 knockdown was investigated in a xenograft mouse model of ovarian cancer. Results: Ovarian cancer tissue exhibited significantly higher E2F8 expression compared to that of normal ovarian tissue. Clinical data showed that E2F8 was a significant predictor of progression-free survival. Moreover, the prognosis of the ovarian cancer patients with high E2F8 expression was poorer than that of the patients with low E2F8 expression. In vitro experiments using E2F8-knockdown ovarian cancer cell lines demonstrated that E2F8 knockdown inhibited cell proliferation, migration, and tumor invasion. Additionally, E2F8 was a potent inducer and modulator of the expression of epithelial–mesenchymal transition and Notch signaling pathway-related markers. We confirmed the function of E2F8 in vivo, signifying that E2F8 knockdown was significantly correlated with reduced tumor size and weight. Conclusions: Our findings indicate that E2F8 is highly correlated with ovarian cancer progression. Hence, E2F8 can be utilized as a prognostic marker and therapeutic target against ovarian malignancy.

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“…We also found that upregulation of E2F1/2/7/8 is an independent prognostic factor for patient OS and that genetic alterations of E2Fs were associated with poor DFS in cervical cancer, indicating that dysregulation of E2F1/2/7/8 may be associated with progression of cervical cancer. Because an oncogenic role of E2F1 and E2F8 in cervical cancer has been reported [24,25], we knocked down E2F2 and E2F7 by shRNA in cells from the cervical cancer cell lines HeLa and C-33 A, and further investigated to assess the effect of E2F2 and E2F7 knockdown on cellular functions of HeLa and C-33 A cells. 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.…”

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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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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E2F8 regulates the proliferation and invasion through epithelial-mesenchymal transition in cervical cancer

Cited by 25 publications

References 26 publications

Musashi1 Contribution to Glioblastoma Development via Regulation of a Network of DNA Replication, Cell Cycle and Division Genes

Musashi1 Contribution to Glioblastoma Development via Regulation of a Network of DNA Replication, Cell Cycle and Division Genes

E2F8 Induces Cell Proliferation and Invasion through the Epithelial–Mesenchymal Transition and Notch Signaling Pathways in Ovarian Cancer

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

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