Repression of engrailed 2 inhibits the proliferation and invasion of human bladder cancer in vitro and in vivo

Li, Yunfei; Liu, Haitao; Lai, Caiyong; Su, Zexuan; Heng, Baoli; Gao, Shuangquan

doi:10.3892/or.2015.3858

Cited by 12 publications

(12 citation statements)

References 48 publications

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“…We found evidence of novel resistance mechanisms as well, although these findings require prospective validation and functional validation. For instance, EN2 expression may play a role in PI3K pathway activation and PTEN inhibition in bladder cancer cells (44). BRSK2 expression may activate Akt and therefore increase the survival of pancreatic ductal adenocarcinoma cells (45).…”

Section: Discussionmentioning

confidence: 99%

Low-pass Whole-genome Sequencing of Circulating Cell-free DNA Demonstrates Dynamic Changes in Genomic Copy Number in a Squamous Lung Cancer Clinical Cohort

Chen¹,

Chang²,

Spoerke³

et al. 2019

Clinical Cancer Research

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Purpose: We developed a method to monitor copy number variations (CNV) in plasma cell-free DNA (cfDNA) from patients with metastatic squamous non-small cell lung cancer (NSCLC). We aimed to explore the association between tumor-derived cfDNA and clinical outcomes, and sought CNVs that may suggest potential resistance mechanisms. Experimental Design: Sensitivity and specificity of low-pass whole-genome sequencing (LP-WGS) were first determined using cell line DNA and cfDNA. LP-WGS was performed on baseline and longitudinal cfDNA of 152 patients with squamous NSCLC treated with chemotherapy, or in combination with pictilisib, a pan-PI3K inhibitor. cfDNA tumor fraction and detected CNVs were analyzed in association with clinical outcomes. Results: LP-WGS successfully detected CNVs in cfDNA with tumor fraction !10%, which represented approximately 30% of the first-line NSCLC patients in this study. The most frequent CNVs were gains in chromosome 3q, which harbors the PIK3CA and SOX2 oncogenes. The CNV landscape in cfDNA with a high tumor fraction generally matched that of corresponding tumor tissue. Tumor fraction in cfDNA was dynamic during treatment, and increases in tumor fraction and corresponding CNVs could be detected before radiographic progression in 7 of 12 patients. Recurrent CNVs, such as MYC amplification, were enriched in cfDNA from posttreatment samples compared with the baseline, suggesting a potential resistance mechanism to pictilisib. Conclusions: LP-WGS offers an unbiased and highthroughput way to investigate CNVs and tumor fraction in cfDNA of patients with cancer. It may also be valuable for monitoring treatment response, detecting disease progression early, and identifying emergent clones associated with therapeutic resistance.

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Section: Discussionmentioning

confidence: 99%

Low-pass Whole-genome Sequencing of Circulating Cell-free DNA Demonstrates Dynamic Changes in Genomic Copy Number in a Squamous Lung Cancer Clinical Cohort

Chen¹,

Chang²,

Spoerke³

et al. 2019

Clinical Cancer Research

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“…Previous reports confirmed that EN2 contributed to breast cancer as an oncogene (5). More recently, studies have demonstrated that EN2 also plays a role in prostate cancer and BC (6,7). Our previous study indicated that EN2 could activate the PI3K/Akt pathway while inhibiting PTEN as a substitutable cancer gene in BC, and could potentially cure BC in targeted therapies (7).…”

mentioning

confidence: 64%

“…More recently, studies have demonstrated that EN2 also plays a role in prostate cancer and BC (6,7). Our previous study indicated that EN2 could activate the PI3K/Akt pathway while inhibiting PTEN as a substitutable cancer gene in BC, and could potentially cure BC in targeted therapies (7). In addition, the high level of EN2 expression is related to the grade, as well as the stage, of BC in pathology.…”

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confidence: 99%

microRNA-27b inhibits cell proliferation and invasion in bladder cancer by targeting engrailed-2

Duan

Gan

et al. 2021

Bioscience Reports

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Background: Bladder cancer is considered a malignant tumour characterised by great heterogeneity. Engrailed-2 may be a gene implicated in bladder cancer. Bioinformatics analysis found base pair complementation between microRNA-27b and engrailed-2. The present study aimed to investigate the reciprocal association between microRNA-27b and engrailed-2 in bladder cancer. Methods: The microRNA-27b and the protein of engrailed-2 in the tissues and cells of the bladder were detected. The processes of apoptosis, proliferation, invasion, and migration of tumour cells were evaluated. The co-action between microRNA-27b and engrailed-2 was detected by a luciferase reporter system. Finally, the interaction between microRNA-27b and engrailed-2 was further verified in vivo. Results: The study found that the expression level of microRNA-27b is lower in bladder cancer tissues and cells than that in neighbouring ordinary tissues, whereas the opposite outcome was observed regarding the expression level of engrailed-2. Furthermore, microRNA-27b expression level is not significantly linked to the age of patients with bladder cancer; however, it is significantly associated with the clinicopathological grade of bladder cancer. Notably, engrailed-2 is negatively regulated by microRNA-27b. Transfection with microRNA-27b was associated with a significant reduction in the activity of bladder cancer cells and promoted apoptosis, while engrailed-2 restoration effectively reversed the above effects of microRNA-27b on bladder cancer in vitro and in vivo. Conclusions: In conclusion, engrailed-2 is engaged in the development and process of bladder cancer through the negative mediation of microRNA-27b; additionally, microRNA-27b/engrailed-2 could form a signalling pathway with a significant effect on the process of bladder cancer.

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“…Recent studies have shown that homeobox-containing genes, including HOX, EMX, PAX, EN, and so on, as key regulators contribute to the development and progression of a variety of human cancers 3 , 18 , 19 . As the human engrailed homolog, EN2 has been reported to correlate closely with human cancers such as prostate, breast, bladder, ovarian cancer, and non -small cell lung cancer 6 – 8 , 20 , 21 . However, it remains unclear whether EN2 has any role in colorectal cancer.…”

Section: Discussionmentioning

confidence: 99%

EN2 as an oncogene promotes tumor progression via regulating CCL20 in colorectal cancer

Liu

Xiao

et al. 2020

Cell Death Dis

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Engrailed-2 (EN2), a member of the engrailed homeobox family, has been shown to be abnormally expressed in a variety of cancers. However, the expression and the clinical significance of EN2 in colorectal cancer (CRC) are largely unknown. Firstly, we found that EN2 acted as an oncogene in CRC. EN2 was upregulated in colorectal cancer tissues compared with adjacent normal tissues. Higher EN2 expression was significantly associated with poorer survival rate. Knockdown of EN2 markedly inhibited proliferation and migration capacities of SW480 cells in vitro, and suppressed tumorigenicity in vivo. Mechanistically, Chemokine ligand 20 (CCL20), a member of the CC motif chemokine subfamily, was identified as a direct target gene of EN2 in CRC. CCL20 expression was positively correlated with EN2 expression in CRC tissues. Moreover, EN2 promoted the proliferation and migration of CRC cells by regulating the expression of CCL20 in vitro. These results suggest that EN2 plays a critical role in the CRC tumor progression and may serve as a potential target for CRC prevention and therapy.

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Repression of engrailed 2 inhibits the proliferation and invasion of human bladder cancer in vitro and in vivo

Cited by 12 publications

References 48 publications

Low-pass Whole-genome Sequencing of Circulating Cell-free DNA Demonstrates Dynamic Changes in Genomic Copy Number in a Squamous Lung Cancer Clinical Cohort

Low-pass Whole-genome Sequencing of Circulating Cell-free DNA Demonstrates Dynamic Changes in Genomic Copy Number in a Squamous Lung Cancer Clinical Cohort

microRNA-27b inhibits cell proliferation and invasion in bladder cancer by targeting engrailed-2

EN2 as an oncogene promotes tumor progression via regulating CCL20 in colorectal cancer

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