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

Karol Czubak; Marzena Anna Lewandowska; Katarzyna Klonowska; Krzysztof Roszkowski; Janusz Kowalewski; Marek Figlerowicz; Piotr Kozlowski

doi:10.18632/oncotarget.4351

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Research Papers:

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

Karol Czubak, Marzena Anna Lewandowska, Katarzyna Klonowska, Krzysztof Roszkowski, Janusz Kowalewski, Marek Figlerowicz and Piotr Kozlowski _

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Oncotarget. 2015; 6:23399-23416. https://doi.org/10.18632/oncotarget.4351

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Abstract

Karol Czubak1, Marzena Anna Lewandowska2,3, Katarzyna Klonowska1, Krzysztof Roszkowski4,5, Janusz Kowalewski3,6, Marek Figlerowicz1, Piotr Kozlowski1

1European Centre for Bioinformatics and Genomics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland

2Molecular Oncology and Genetics Department, Innovative Medical Forum, The Franciszek Lukaszczyk Oncology Center, Bydgoszcz, Poland

3Department of Thoracic Surgery and Tumors, Nicolaus Copernicus University, Torun, Collegium Medicum, Bydgoszcz, Poland

4Department of Radiotherapy, The Franciszek Lukaszczyk Oncology Center, Bydgoszcz, Poland

5Department of Oncology, Radiotherapy and Gynecologic Oncology, Nicolaus Copernicus University, Torun, Collegium Medicum, Bydgoszcz, Poland

6Department of Thoracic Surgery and Tumors, The Franciszek Lukaszczyk Oncology Center, Bydgoszcz, Poland

Correspondence to:

Piotr Kozlowski, e-mail: [email protected]; [email protected]

Keywords: microRNA, DROSHA, DICER1, non-small cell lung cancer NSCLC, MLPA

Received: May 04, 2015 Accepted: June 08, 2015 Published: June 22, 2015

ABSTRACT

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.

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Research Papers:

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

Abstract