High copy number variation of cancer-related microRNA genes and frequent amplification ofDICER1andDROSHAin lung cancer

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// Karol Czubak 1 , Marzena Anna Lewandowska 2, 3 , Katarzyna Klonowska 1 , Krzysztof Roszkowski 4, 5 , Janusz Kowalewski 3, 6 , Marek Figlerowicz 1 , Piotr Kozlowski 1 1 European Centre for Bioinformatics and Genomics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland 2 Molecular Oncology and Genetics Department, Innovative Medical Forum, The Franciszek Lukaszczyk Oncology Center, Bydgoszcz, Poland 3 Department of Thoracic Surgery and Tumors, Nicolaus Copernicus University, Torun, Collegium Medicum, Bydgoszcz, Poland 4 Department of Radiotherapy, The Franciszek Lukaszczyk Oncology Center, Bydgoszcz, Poland 5 Department of Oncology, Radiotherapy and Gynecologic Oncology, Nicolaus Copernicus University, Torun, Collegium Medicum, Bydgoszcz, Poland 6 Department of Thoracic Surgery and Tumors, The Franciszek Lukaszczyk Oncology Center, Bydgoszcz, Poland Correspondence to: Piotr Kozlowski, e-mail: kozlowp@yahoo.com ; kozlowp@ibch.poznan.pl 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 .