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Published on: May 16, 2012
The microRNA-processing enzymes: Drosha and Dicer can predict prognosis of nasopharyngeal carcinoma
Xiaofang Guo1, Qianjin Liao, Pan Chen
1Cancer Research Institute, Central South University, 110 Xiang-Ya Road, Changsha, 410078, Hunan, People's Republic of China.
Purpose:
Dysregulation of microRNA (miRNA) metabolism has been observed in a variety of human cancers, but the expression patterns of the enzymes responsible for generating miRNAs remain largely unexplored. In this study, we investigated the expression profiles of the two most important enzymes of the miRNA machinery, Drosha and Dicer, which were closely correlated with nasopharyngeal carcinoma (NPC) and patient survival.
Methods:
Dicer and Drosha mRNA levels were detected by quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) using 24 NPC tissues, 7 normal nasopharyngeal epithelium samples (NPE) and NPC cell lines. In addition, protein levels were detected by immunohistochemistry (IHC) using an NPC tissue microarray (TMA), which include 251 NPC and 105 NPE cases. For some NPC patients can not be contacted, the survival data were available only for 146 patients. Kaplan-Meier analysis was performed, and the chi-square and log-rank tests were used to detect significance levels using SPSS 15.0 software.
Results:
The mean level of Dicer and Drosha mRNA were significantly down-regulated in NPC tissue specimens and cell lines when compared with controls. The low levels of Dicer and Drosha protein were frequently seen in NPC, and the low expression of Dicer and Drosha protein was significantly correlated with shorter progression-free survival (PFS) and overall survival (OS) of NPC patients.
Conclusions:
We observed that Drosha and Dicer expression was dysregulation in NPC compared with healthy control samples and was significantly correlated with shorter PFS and OS of NPC patients. Therefore, we hypothesise that the expression levels of Dicer and Drosha could be used as potential prognostic biomarkers for NPC.
Insights
Low levels of Drosha and Dicer enzymes, crucial for microRNA (miRNA) generation, are linked to nasopharyngeal carcinoma (NPC). This suggests Drosha and Dicer expression may serve as prognostic biomarkers for NPC patients.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- MicroRNA (miRNA) metabolism is dysregulated in various human cancers.
- Enzyme expression patterns in miRNA generation are underexplored in nasopharyngeal carcinoma (NPC).
Purpose of the Study:
- To investigate the expression profiles of Drosha and Dicer in NPC.
- To determine the correlation between Drosha and Dicer expression and NPC patient survival.
Main Methods:
- Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) for mRNA levels in NPC tissues and cell lines.
- Immunohistochemistry (IHC) on a tissue microarray (TMA) for protein levels in 251 NPC and 105 normal nasopharyngeal epithelium (NPE) cases.
- Kaplan-Meier analysis for survival data of 146 NPC patients.
Main Results:
- Dicer and Drosha mRNA levels were significantly down-regulated in NPC tissues and cell lines compared to controls.
- Low Dicer and Drosha protein expression was frequently observed in NPC.
- Reduced Dicer and Drosha protein levels correlated significantly with shorter progression-free survival (PFS) and overall survival (OS).
Conclusions:
- Drosha and Dicer expression is dysregulated in NPC compared to healthy controls.
- Expression levels of Drosha and Dicer are significantly associated with poorer PFS and OS in NPC patients.
- Drosha and Dicer may serve as potential prognostic biomarkers for NPC.
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