|The downregulation of PRDM1/Blimp-1 is associated with aberrant expression of miR-223 in extranodal NK/T-cell lymphoma, nasal type|
|Liang, Li1; Nong, Lin1; Zhang, Shuang1; Zhao, Jing1; Ti, Hongjuan2; Dong, Ying1; Zhang, Bo3; Li, Ting1|
|关键词||Extranodal NK/T-cell lymphoma Nasal type PRDM1 miR-223|
|刊名||JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH|
|WOS标题词||Science & Technology|
|关键词[WOS]||TUMOR-SUPPRESSOR GENE ; COMPARATIVE GENOMIC HYBRIDIZATION ; ACUTE MYELOID-LEUKEMIA ; B-CELL ; TRANSCRIPTION FACTOR ; MICRORNA-223 ; DIFFERENTIATION ; PATHOGENESIS ; PRDM1 ; LINE|
Background: The mechanism for inactivation of positive regulatory domain containing I (PRDM1), a newly identified tumour suppressor gene in extranodal NK/T-cell lymphoma, nasal type (EN-NK/T-NT) has not been well defined. The aim of the present study was to investigate the expression of PRDM1 in EN-NK/T-NT and analyse its downregulation by miRNAs.
Methods: PRDM1 and miRNA expression were evaluated in EN-NK/T-NT samples by immunohistochemical analysis, qRT-PCR, and in situ hybridisation. Luciferase assays were performed to verify the direct binding of miR-223 to the 3′-untranslated region of PRDM1 mRNA. In addition, the effect of miR-223 on PRDM1 expression was assessed in NK/T lymphoma cell lines by transfecting a miR-223 mimic or inhibitor to increase or decrease the effective expression of miR-223. Overall survival and failure-free survival in EN-NK/T-NT patients were analysed using Kaplan-Meier single-factor analysis and the log-rank test.
Results: Investigation of the downregulation of PRDM1 in EN-NK/T-NT cases revealed that PRDM1-positive staining might be a favourable predictor of overall survival and failure-free survival in EN-NK/T-NT patients. However, the negative staining of PRDM1 usually presented transcripts, suggesting a possible post-transcriptional regulation. miR-223 and its putative target gene, PRDM1, exhibited opposite patterns of expression in EN-NK/T-NT tissues and cell lines. Moreover, PRDM1 was identified as a direct target gene of miR-223 by luciferase assays. The ectopic expression of miR-223 led to the downregulation of the PRDM1 protein in the NK/T-cell lymphoma cell line, whereas a decrease in miR-223 restored the level of PRDM1 protein.
Conclusions: Our findings reveal that the downregulation of the tumour suppressor PRDM1 in EN-NK/T-NT samples is mediated by miR-223 and that PRDM1-positive staining might have prognostic value for evaluating the clinical outcome of EN-NK/T-NT patients.
|资助机构||National Natural Sciences Foundation of China, Beijing|
|作者单位||1.Haidian Hosp Beijing, Dept Pathol, Beijing 100080, Peoples R China|
2.Peking Univ, Hosp 1, Dept Pathol, Beijing 100034, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Dept Pathol, Beijing 100191, Peoples R China
|Liang, Li,Nong, Lin,Zhang, Shuang,et al. The downregulation of PRDM1/Blimp-1 is associated with aberrant expression of miR-223 in extranodal NK/T-cell lymphoma, nasal type[J]. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,2014,33.|
|APA||Liang, Li.,Nong, Lin.,Zhang, Shuang.,Zhao, Jing.,Ti, Hongjuan.,...&Li, Ting.(2014).The downregulation of PRDM1/Blimp-1 is associated with aberrant expression of miR-223 in extranodal NK/T-cell lymphoma, nasal type.JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,33.|
|MLA||Liang, Li,et al."The downregulation of PRDM1/Blimp-1 is associated with aberrant expression of miR-223 in extranodal NK/T-cell lymphoma, nasal type".JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 33(2014).|