A potential oncogenic role of the commonly observed E2F5 overexpression in hepatocellular carcinoma

Jiang, Yuzhu; Yim, Seon‐Hee; Xu, Haidong; Jung, Seung‐Hyun; Yang, So Young; Hu, Hae‐Jin; Jung, Chan-Kwon; Chung, Yeun‐Jun

doi:10.3748/wjg.v17.i4.470

Cited by 50 publications

(49 citation statements)

References 19 publications

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“…The transcription factor E2F performs a central role in cell growth and proliferation by controlling cell cycle (26), which suggests that E2F5 may also be involved in cellular proliferation and cell cycle progression as an important member of the E2F family. Previous data has reported that E2F5 was overexpressed in various types of human cancer including breast, epithelial ovarian and prostate cancer and hepatocellular carcinoma, and closely associated with cancer progression and prognosis (16)(17)(18)(19). However, the role of E2F5 in GC remained unclear.…”

Section: Discussionmentioning

confidence: 98%

“…As demonstrated in Fig. 3A, E2F transcription factor 5 protein (E2F5) was identified as an interesting candidate, as E2F5 has previously been observed as overexpressed in various types of cancer, including breast (16), epithelial ovarian (17), prostate cancer (18) and hepatocellular carcinoma (19), and is involved in cellular proliferation, cell growth and cell cycle progression. To investigate whether miRNA-34a is capable of regulating E2F5 expression in GC cells, qPCR was used.…”

Section: E2f5 Is a Direct Target Of Mirna-34amentioning

confidence: 99%

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miRNA-34a enhances the sensitivity of gastric cancer cells to treatment with paclitaxel by targeting E2F5

Zhao

2017

Oncology Letters

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Abstract. Gastric cancer (GC) is one of the most common types of malignant cancer worldwide, however improvements are required to the current therapies for GC. Although paclitaxel is one of the most promising chemotherapeutic agents in clinical use for GC, the resistance to paclitaxel that develops during treatment is a major obstacle to further treatments of GC. The present study reports that micro (mi) RNA-34a, a tumor suppressor in various types of cancer, may be an important regulator of chemoresistance in GC, as miRNA-34a mimics and inhibitors, enhance and inhibit the chemotherapeutic efficacy of paclitaxel, respectively. In addition, the present study identified that E2F transcription factor 5 (E2F5), a key oncogenic protein, is the direct target candidate of miRNA-34a. Previous studies have demonstrated that the inhibition of E2F5 by specific E2F5 small interfering RNA also increases the sensitivity of GC cells to paclitaxel. In conclusion, the present data suggest that miRNA-34a enhances the treatment of sensitive GC cells to paclitaxel by targeting E2F5. Therefore, the miRNA-34a/E2F5 axis appears to be a potential promising therapeutic target for overcoming the chemotherapeutic resistance of GC.

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Section: Discussionmentioning

confidence: 98%

Section: E2f5 Is a Direct Target Of Mirna-34amentioning

confidence: 99%

miRNA-34a enhances the sensitivity of gastric cancer cells to treatment with paclitaxel by targeting E2F5

Zhao

2017

Oncology Letters

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“…The present study implies that E2F5 as other E2Fs plays a vital role in apoptosis, senescence, proliferation, the DNA-damage response and DNA repair [11]. Jiang Y determined that E2F5 is commonly upregulated in HCC and that E2F5 knockdown significantly inhibits the growth of HCC cells [10]. However, the upstream mechanism that regulates E2F5 in HCC remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

“…E2F belongs to a family of transcription factors and was named for its function; E2F regulates transcription by binding to a common sequence (TTTSSCGC: S = C or G) known as an E2F site [9]. E2F5 is a member of the E2F family and regulates the expression of genes involved in cell cycle control by directly binding to the promoters of these genes [10]. The present study implies that E2F5 as other E2Fs plays a vital role in apoptosis, senescence, proliferation, the DNA-damage response and DNA repair [11].…”

Section: Introductionmentioning

confidence: 99%

The transcription factor FOXN3 inhibits cell proliferation by downregulating E2F5 expression in hepatocellular carcinoma cells

Sun

et al. 2016

Oncotarget

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Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide, and the mechanisms underlying the development of HCC remain to be elucidated. Forkhead box N3 (FOXN3) is an important member of the FOX family of transcription factors that plays an essential role in several cancers but has not been investigated in HCC. In this study, we demonstrate that FOXN3 is downregulated in human primary HCC tissues compared with their matched adjacent liver tissues. Functional tests of FOXN3 demonstrated that FOXN3 inhibits the proliferation of HCC cells in vitro and in vivo. Additionally, FOXN3 repressed the mRNA and protein expression of E2F5, a reported potential oncogene, by inhibiting the promoter activity of E2F5. Collectively, our findings indicate that FOXN3 functions as a tumor suppressor in HCC by downregulating the expression of E2F5.

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“…Moreover, dual-luciferase assay determined that E2F5 is a direct target of miR-154-5p. Amplification of the E2F5 gene has been frequently observed in various malignant tumors [5,6,11,12] . The DNA qPCR, Western blot analysis and immunohistochemical staining both found the significant higher expression of E2F5 proteins in PCa tissues than those in adjacent benign specimens, and the overexpression of E2F5 protein was significantly associated with a high Gleason score and an advanced clinical stage [7] .…”

Section: E2f5 Is a Direct Target Gene Of Mir-154-5pmentioning

confidence: 99%

miRNA-154-5p Inhibits Proliferation, Migration and Invasion by Targeting E2F5 in Prostate Cancer Cell Lines

Zheng

Zhu²,

Ma³

et al. 2016

Urol Int

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Background: MicroRNAs (miRNAs) are a class of small non-coding RNAs (18-25 nucleotides) which post-transcriptionally regulate gene expression by negatively regulating the stability or translational efficiency of their target mRNAs. This study aimed to determine the function of miR-154-5p in prostate cancer (PCa) cells and identify the novel molecular targets regulated by miR-154-5p. Materials and Methods: The effects of forced miR-154-5p expression or E2F transcription factor 5 (E2F5) knockdown on PCa cells were evaluated by cell proliferation, flow cytometry, cell migration and invasion assays as well as by Western blot analysis. Dual-luciferase reporter assay was performed to verify the precise target of miR-154-5p. Results: The forced expression of miR-154-5p or E2F5 knockdown significantly restrained cell growth, as well as the migratory and invasive capabilities. Such expression also induced G₁ cell cycle arrest of PCa cells in vitro. Hence, E2F5 is a direct target gene of miR-154-5p. Conclusions: miR-154-5p may play an important role as an inhibitor of proliferation, migration and invasion of PCa by targeting E2F5 in PCa cell lines.

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A potential oncogenic role of the commonly observed E2F5 overexpression in hepatocellular carcinoma

Abstract: To our knowledge, this is the first evidence that E2F5 is commonly overexpressed in primary HCC and that E2F5 knockdown significantly repressed the growth of HCC cells.

Cited by 50 publications

References 19 publications

miRNA-34a enhances the sensitivity of gastric cancer cells to treatment with paclitaxel by targeting E2F5

miRNA-34a enhances the sensitivity of gastric cancer cells to treatment with paclitaxel by targeting E2F5

The transcription factor FOXN3 inhibits cell proliferation by downregulating E2F5 expression in hepatocellular carcinoma cells

miRNA-154-5p Inhibits Proliferation, Migration and Invasion by Targeting E2F5 in Prostate Cancer Cell Lines

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