Hypermethylation of the<i>GABRE∼miR-452∼miR-224</i>Promoter in Prostate Cancer Predicts Biochemical Recurrence after Radical Prostatectomy

Kristensen, Helle; Haldrup, Christa; Strand, Siri H.; Mundbjerg, Kamilla; Mortensen, Martin M.; Thorsen, Kasper; Ostenfeld, Marie Stampe; Wild, Peter J.; Arsov, Christian; Goering, Wolfgang; Visakorpi, Tapio; Egevad, Lars; Lindberg, Johan; Grönberg, Henrik; Høyer, Søren; Borre, Michael; Ørntoft, Torben F.; Sørensen, Karina Dalsgaard

doi:10.1158/1078-0432.ccr-13-2642

Cited by 89 publications

(114 citation statements)

References 48 publications

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“…In addition, the expression levels of miR-452 were lower in all examined breast cancer cell lines than in the human breast epithelial cell line MCF-10A. Similar results have been reported for non-small cell lung cancer (24), prostate cancer (25) and glioma (26). These findings suggest that the low expression of miR-452 may be a common event in human cancer, and may be associated with metastasis of breast cancer.…”

Section: Discussionsupporting

confidence: 83%

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Tumor-suppressive microRNA-452 inhibits migration and invasion of breast cancer cells by directly targeting RAB11A

Fan

et al. 2017

Oncology Letters

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Abstract. Breast cancer is the most common type of malignant tumor in females, and metastasis is the most common cause of breast cancer-associated mortality. Previous studies have identified that abnormal expression of microRNAs is commonly observed in human cancer and may be crucial for cancer metastasis. In the present study, microRNA-452 (miR-452) was investigated for its ability to act as a tumor suppressor in breast cancer. miR-452 expression was quantified in breast cancer tissue samples and cell lines with reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Transwell migration and invasion assays were used to investigate the effect of miR-452 on the migration and invasion capabilities of breast cancer cells. Potential target genes of miR-452 were identified with miRanda and TargetScan. A luciferase reporter assay was performed to validate RAB11A as a putative target of miR-452, and was corroborated by RT-qPCR and western blot analyses. Finally, small interfering RNA (siRNA) was used to knockdown RAB11A expression and confirm whether miR-452 inhibited breast cancer cell migration and invasion via the negative regulation of RAB11A. The results revealed that miR-452 was downregulated in breast cancer tissues and cell lines, and that its downregulation may be associated with breast cancer metastasis, as miR-452 expression inhibited the migration and invasion capacities of breast cancer cells. RT-qPCR and western blot analyses indicated that miR-452 negatively regulated the expression of RAB11A mRNA and protein. The luciferase reporter assay revealed that miR-452 specifically bound to the 3'-untranslated region of RAB11A. Furthermore, inhibition of RAB11A with siRNA inhibited breast cancer cell migration and invasion. In conclusion, the present study has demonstrated that miR-452 may act as a tumor suppressor gene via inhibition of cell migration and invasion by targeting RAB11A in breast cancer.

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Section: Discussionsupporting

confidence: 83%

“…miR-452 has been reported to be abnormally expressed in numerous types of human cancer (24)(25)(26). However, no specific studies have been performed to reveal the expression and biological roles underlying miR-452 in breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Tumor-suppressive microRNA-452 inhibits migration and invasion of breast cancer cells by directly targeting RAB11A

Fan

et al. 2017

Oncology Letters

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“…However, miR-452 expression in malignant tumors is controversial. Although miR-452 was also found to be downregulated in a variety of malignancies such as prostate cancer (18), breast cancer (19) and glioma (20), this miRNA was highly expressed in esophageal cancer (21) and urothelial carcinoma (22), as well as in hepatocellular carcinoma (23). Our previous study has documented that miR-452 expression was down-regulated in human NSCLC tissues compared with the corresponding adjacent tissues (11).…”

Section: Discussionmentioning

confidence: 96%

“…These stemness regulators reduced stem-like traits tumorigenesis (20). Furthermore, functional studies suggested that miR-452 inhibited proliferation, migration and invasion of prostate cancer cells via regulation of pathways of cell cycle and cellular adhesion and motility, and finally associated biochemical recurrence (18). In our previous study, we found that higher expression of miR-452 could inhibit NSCLC cell invasion and metastasis capability by modulating BMI1 expression, suggesting that miR-452 plays an important role in development of NSCLC (11).…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of miR-452 is associated with poor prognosis in the non-small-cell lung cancer

He¹,

Xia²,

Liu³

et al. 2016

J. Thorac. Dis.

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Background: Non-small cell lung cancer (NSCLC) remains the most life-threatening cancer in the world. The aim of the current study was to investigate the value of miR-452 for the prognosis of patients with NSCLC. Methods: Real-time quantitative PCR (qRT-PCR) was used to test the expression level of miR-452 in 161 paired clinical NSCLC tissues and their adjacent tissues. Survival curves were made and the log rank test was used to analyze the survival difference between both groups with higher and lower expression level of miR-452. Univariate and multivariate Cox regression analyses were finally used to determine the independent factors for overall survival (OS) and disease-free survival (DFS) times. Results: The miR-452 expressions in tumor samples (n=161) were comparably lower than those in the adjacent tissues. miR-452 expression levels were significantly associated with tumor differentiation grade, tumor size and lymph nodes metastasis. Furthermore, Kaplan-Meier survival curves showed that patients with higher expression of miR-452 was confirmed to have more favorable OS (P=0.004) and DFS (P=0.026).Multivariate survival analysis verified that miR-452 expression level, as well as lymph nodes metastasis, was an independent predictor of both OS and DFS for NSCLC patients. Conclusions: Our study demonstrated that miR-452 functioned as a novel diagnostic biomarker and a promising prognostic predictor for NSCLC patients.

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“…Previous studies have reported that miR-452-5p expressions in different neoplasms are distinct, which is upregulated in urinary tract epithelial tumors, esophageal cancer, and liver cancer, [18][19][20] but downregulated in breast cancer, prostate cancer, and glioma. [21][22][23] Currently, there have been only a few reports regarding the relationship between miR-452-5p and lung cancer. The clinical significance and possible molecular function (MF) of miR-452-5p in NSCLC was reported by Zhang et al 24 and He et al 25,26 However, clinical samples in their research were restricted by region and quantity, and the complicated mechanism of miR-452-5p in LUAD remained unclear.…”

Section: Introductionmentioning

confidence: 99%

Clinical value of miR-452-5p expression in lung adenocarcinoma: A retrospective quantitative real-time polymerase chain reaction study and verification based on The Cancer Genome Atlas and Gene Expression Omnibus databases

et al. 2017

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The role and mechanism of miR-452-5p in lung adenocarcinoma remain unclear. In this study, we performed a systematic study to investigate the clinical value of miR-452-5p expression in lung adenocarcinoma. The expression of miR-452-5p in 101 lung adenocarcinoma patients was detected by quantitative real-time polymerase chain reaction. The Cancer Genome Atlas and Gene Expression Omnibus databases were joined to verify the expression level of miR-452-5p in lung adenocarcinoma. Via several online prediction databases and bioinformatics software, pathway and network analyses of miR-452-5p target genes were performed to explore its prospective molecular mechanism. The expression of miR-452-5p in lung adenocarcinoma in house was significantly lower than that in adjacent tissues (p < 0.001). Additionally, the expression level of miR-452-5p was negatively correlated with several clinicopathological parameters including the tumor size (p = 0.014), lymph node metastasis (p = 0.032), and tumor-node-metastasis stage (p = 0.036). Data from The Cancer Genome Atlas also confirmed the low expression of miR-452 in lung adenocarcinoma (p < 0.001). Furthermore, reduced expression of miR-452-5p in lung adenocarcinoma (standard mean deviations = −0.393, 95% confidence interval: −0.774 to −0.011, p = 0.044) was validated by a meta-analysis. Five hub genes targeted by miR-452-5p, including SMAD family member 4, SMAD family member 2, cyclin-dependent kinase inhibitor 1B, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon, and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta, were significantly enriched in the cell-cycle pathway. In conclusion, low expression of miR-452-5p tends to play an essential role in lung adenocarcinoma. Bioinformatics analysis might be beneficial to reveal the potential mechanism of miR-452-5p in lung adenocarcinoma.

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Hypermethylation of theGABRE∼miR-452∼miR-224Promoter in Prostate Cancer Predicts Biochemical Recurrence after Radical Prostatectomy

Cited by 89 publications

References 48 publications

Tumor-suppressive microRNA-452 inhibits migration and invasion of breast cancer cells by directly targeting RAB11A

Tumor-suppressive microRNA-452 inhibits migration and invasion of breast cancer cells by directly targeting RAB11A

Down-regulation of miR-452 is associated with poor prognosis in the non-small-cell lung cancer

Clinical value of miR-452-5p expression in lung adenocarcinoma: A retrospective quantitative real-time polymerase chain reaction study and verification based on The Cancer Genome Atlas and Gene Expression Omnibus databases

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