High copy number variation of cancer-related microRNA genes and frequent amplification of DICER1 and DROSHA in lung cancer

被引：56

作者：

Czubak, Karol ^{[1
]}

Lewandowska, Marzena Anna ^{[2
,3
]}

Klonowska, Katarzyna ^{[1
]}

Roszkowski, Krzysztof ^{[4
,5
]}

Kowalewski, Janusz ^{[3
,6
]}

Figlerowicz, Marek ^{[1
]}

Kozlowski, Piotr ^{[1
]}

机构：

[1] Polish Acad Sci, Inst Bioorgan Chem, European Ctr Bioinformat & Genom, Poznan, Poland

[2] Franciszek Lukaszczyk Oncol Ctr, Innovat Med Forum, Mol Oncol & Genet Dept, Bydgoszcz, Poland

[3] Nicolaus Copernicus Univ, Coll Med, Dept Thorac Surg & Tumors, Torun, Bydgoszcz, Poland

[4] Franciszek Lukaszczyk Oncol Ctr, Dept Radiotherapy, Bydgoszcz, Poland

[5] Nicolaus Copernicus Univ, Coll Med, Dept Oncol Radiotherapy & Gynecol Oncol, Torun, Bydgoszcz, Poland

[6] Franciszek Lukaszczyk Oncol Ctr, Dept Thorac Surg & Tumors, Bydgoszcz, Poland

来源：

ONCOTARGET | 2015年 / 6卷 / 27期

关键词：

microRNA; DROSHA; DICER1; non-small cell lung cancer NSCLC; MLPA; SOMATIC MUTATIONS; BREAST-CANCER; GENOMIC ALTERATIONS; CELL-PROLIFERATION; EXPRESSION LEVELS; POOR-PROGNOSIS; IDENTIFICATION; ADENOCARCINOMA; BIOMARKERS; SURVIVAL;

D O I：

10.18632/oncotarget.4351

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

A growing body of evidence indicates that miRNAs may be a class of genetic elements that can either drive or suppress oncogenesis. In this study we analyzed the somatic copy number variation of 14 miRNA genes frequently found to be either over-or underexpressed in lung cancer, as well as two miRNA biogenesis genes, DICER1 and DROSHA, in non-small-cell lung cancer (NSCLC). Our analysis showed that most analyzed miRNA genes undergo substantial copy number alteration in lung cancer. The most frequently amplified miRNA genes include the following: miR-30d, miR-21, miR-17 and miR-155. We also showed that both DICER1 and DROSHA are frequently amplified in NSCLC. The copy number variation of DICER1 and DROSHA correlates well with their expression and survival of NSCLC and other cancer patients. The increased expression of DROSHA and DICER1 decreases and increases the survival, respectively. In conclusion, our results show that copy number variation may be an important mechanism of upregulation/downregulation of miRNAs in cancer and suggest an oncogenic role for DROSHA.

引用

页码：23399 / 23416

页数：18

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