Engrailed-2 might play an anti-oncogenic role in clear-cell renal cell carcinoma

Lai, Caiyong; Xu, Yunjie; Yu, Ganshen; Wu, Xun; Li, Yunfei; Pan, Bin; Heng, Baoli; Xue, Yi-Jun; Su, Zexuan

doi:10.1007/s10735-016-9665-4

Cited by 13 publications

(11 citation statements)

References 22 publications

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“…In another study by the present authors, EN2 expression was inhibited in HK-2 cells using lentivirus-mediated transfection, and overexpression of EN2 in 786-O cells was induced via plasmid transfection (26). Following the inhibition of the EN2 gene, proliferation and invasion of HK-2 cells were promoted.…”

Section: No Of Patients Withmentioning

confidence: 68%

“…However the inhibition of the EN2 gene also resulted in a shortened cell cycle and inhibition of apoptosis. By contrast, overexpression of EN2 gene was able to promote apoptosis and reduce invasive ability and suppress proliferative ability of 786-O cells (26). These findings indicated that EN2 may have an anti-oncogenic function in cc-RCC.…”

Section: No Of Patients Withmentioning

confidence: 83%

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Engrailed‑2 promoter hyper‑methylation is associated with its downregulation in clear cell renal cell carcinoma

Lai

et al. 2017

Oncol Lett

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Abstract. In a previous study by the present authors, it was identified that the expression of engrailed-2 (EN2) gene was downregulated in clear cell renal cell carcinoma (cc-RCC). The aim of the present study was to determine whether aberrant methylation was the mechanism underlying the silencing of EN2 gene in cc-RCC. A total of forty paired cc-RCC tissues, four cc-RCC cell lines and one normal human proximal tubule epithelial cell line were evaluated for EN2 gene methylation status using methylation-specific polymerase chain reaction (PCR). Following treatment with 5-Aza-dc, reverse transcription-quantitative PCR and western blot analysis were performed to examine the expression of EN2. Furthermore, cell proliferation, apoptosis and invasion assays were conducted to analyze the inhibitory effects of EN2 re-expression in 786-O cells. The results of the present study demonstrated that hyper-methylation of EN2 was identified in 12/40 cc-RCC tissues and all cc-RCC cell lines. The methylation status of the EN2 gene was revealed to be associated with histological grade and tumor size in cc-RCC. Following 5-Aza-dc treatment, demethylation of the EN2 gene was identified in 786-O cells, in conjunction with EN2 re-expression. Furthermore, re-activation of the EN2 gene markedly inhibited the proliferative and invasive capacities of cc-RCC. The results of the present study demonstrated that the EN2 gene promoter was hyper-methylated in cc-RCC, which may underlie the silencing of the EN2 gene in cc-RCC.

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Section: No Of Patients Withmentioning

confidence: 68%

Section: No Of Patients Withmentioning

confidence: 83%

Engrailed‑2 promoter hyper‑methylation is associated with its downregulation in clear cell renal cell carcinoma

Lai

et al. 2017

Oncol Lett

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“…EN2 is a member of the homeobox family, which encodes a homeodomain-containing transcription factor that is essential for early development. Elevation of EN2 has been highly correlated with the proliferation, invasion, and migration in several types of malignancies [18][19][20][21][22][23][24][25][26], however, controversial results show that EN2 is silenced in other cancers [27][28][29], and thus EN2 acts as a potential diagnostic and prognostic biomarker [23,[30][31][32][33]. However, decreased EN2 in renal carcinoma has been observed and downregulation of EN2 in 786-O cell line promoted proliferation and reduced apoptosis [27,34,35].…”

Section: Discussionmentioning

confidence: 99%

“…Engrailed-2 (EN2) gene encodes a homeobox-containing transcription factor and participates in the regionalization, patterning and cell differentiation in early brain development [15][16][17]. Accumulated evidence demonstrates that EN2 is highly associated with tumorigenesis in some types of cancers [18][19][20][21][22][23][24][25][26], however, controversial results show that EN2 is silenced in other cancers [27,28]. As for glioma, it remains unclear about EN2 expression pattern and potential functions.…”

Section: Introductionmentioning

confidence: 99%

Engrailed 2 (EN2) acts as a glioma suppressor by inhibiting tumor proliferation/invasion and enhancing sensitivity to temozolomide

Yang

Mao

et al. 2020

Cancer Cell Int

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Background: Glioma is one of the most malignant brain tumors and accounts for the majority of brain cancer related death. Despite progress on mechanistic studies, current understandings of the initiation and progression of glioma are still incomplete. Previous studies demonstrate that Engrailed-2 (EN2), a homeobox-containing transcription factor, is associated with tumorigenesis in a range of cancers heterogeneously, however, the profiles of EN2 expression and its potential functions in gliomas remain unclear. Methods: Real-time PCR was used to identify the expression of EN2 in glioma tissues. To study the biological function of EN2 in glioma, we compared the cell viability and proliferation profiles between EN2 overexpressed and control cells using cell counting kit-8 (CCK8) assay, EdU incorporation assay and colony formation assay. Flow cytometry and Hoechst staining assays were performed to investigate the role of EN2 on glioma cell death. Finally, wound healing and transwell assays were carried out to investigate the role of EN2 on glioma cell invasion. Results: We identified that EN2 was downregulated in human gliomas compared with paired adjacent normal tissues and negatively associated with glioma malignancy. Elevated EN2 expression inhibits cell proliferation, enhances glioma sensitivity to temozolomide and inhibits migration/invasion of glioma cells. Conclusions: Our data identify a novel function of EN2 in glioma suppression and provide potential therapeutic targets for glioma therapy.

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“…Recently, studies have shown that the homeobox (HOX) gene family dysregulation occurs in many types of cancer, including solid and hematological malignancies [8]. A member of the HOX gene family, Engrailed-2 (EN2) has been found to overexpress in various kinds of cancer like PC, breast cancer and bladder cancer and play important roles in oncogenesis [8,9]. And there is evidence showing that the positive detection of EN2 in patients' urine with ELISA was predictive of PC with high sensitivity and specificity (66% and 88.2% respectively) [10].…”

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confidence: 99%

Altered staining patterns and expression level of Engrailed-2 in Benign prostatic hyperplasia and Prostate Cancer predict Prostatic disease progression

Shi

Sa³

et al. 2020

Preprint

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Background: Prostate cancer (PC) as a kind of malignant tumor, causes the most death of cancer among males. Successful curing of PC greatly relies on its diagnose in the early stage. Engrailed-2 (EN2), which has been confirmed being existed in the high level in the urine of PC patients. In this study, we determine if there were differences in the staining patterns and expression level of EN2 in benign prostatic hyperplasia (BPH) and PC.Methods: Immunohistochemical and RT-PCR analysis of the expression of EN2 was conducted in 25 PC and 25 BPH cases. EN2 monoclonal antibody against EN2 helix 3 was developed and its specificity was identified. The subcellular localization of endogenic and exogenous EN2 in three PC cell lines (LNCap, PC3, and DU145) was detected by immunofluorescence. Correlation among clinical indicators and EN2 immunohistochemical scores of these 25 PC and 25 BPH cases were analyzed and two representative PC cases with different EN2 expression were used to vividly illustrate the correlation between EN2 expression and PC clinical stage. Results: The results of western-blotting (WB) and immunofluorescence showed homemade EN2 monoclonal antibody could specifically bind endogenic and ectogenic EN2 protein in three different PC cell lines. Results of immunofluorescence showed the endogenic EN2 was generally expressed in the cytoplasm and ectogenic EN2 has mostly existed in the nucleus of three PC cell lines. Immunohistochemical staining of EN2 in PC was extremely higher than in BPH confirmed by RT-PCR. The staining areas were mostly nucleus and cytoplasm in BPH tissues but cytomembrane in PC tissues. The expression level of EN2 was positively correlated with the PC clinical stage. Conclusion: The EN2 monoclonal antibody we made could be used in immunohistochemistry to display the expression pattern of EN2 in BPH and PC. The staining patterns and expression level of EN2 in BPH and PC are different.

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Engrailed-2 might play an anti-oncogenic role in clear-cell renal cell carcinoma

Cited by 13 publications

References 22 publications

Engrailed‑2 promoter hyper‑methylation is associated with its downregulation in clear cell renal cell carcinoma

Engrailed‑2 promoter hyper‑methylation is associated with its downregulation in clear cell renal cell carcinoma

Engrailed 2 (EN2) acts as a glioma suppressor by inhibiting tumor proliferation/invasion and enhancing sensitivity to temozolomide

Altered staining patterns and expression level of Engrailed-2 in Benign prostatic hyperplasia and Prostate Cancer predict Prostatic disease progression

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