Identification of microRNAs modulated by DNA hypomethylating drugs in extranodal NK/T-cell lymphoma

Abstract

To identify epigenetically silenced miRNAs and to investigate their influences on predictive target oncogenes in extranodal natural killer/T-cell lymphoma (NKTCL). Decitabine treatment was performed to evaluate methylated miRNAs in NKTCL cells. The relationship between a given miRNA and its target mRNA was validated using 24 tumor tissues. miR-379, miR-134, miR-20b, miR-376a, miR-654-3p, miR-143, miR-181c, miR-1225-5p, miR-1246, and miR-1275 were epigenetically silenced in SNK6 cells. miR-134, miR-376a, miR-143 and miR-181c significantly affected cellular viability. PDGFRα was regulated by miR-34a and miR-181c. miR-143, miR-20b and miR34a regulated STAT3 expression. miR-20b and miR-143 expression showed inverse correlations with STAT3 mRNA expression in NKTCL tissues. K-RAS was regulated by miR-181c. Downregulation of cell viability by salirasib treatment was identified. miRNAs were downregulated by DNA methylation, and several microRNAs affected the viability of NKTCL cells. miR-34a and miR-181c may be involved in the oncogenic progression of NKTCL through the regulation of PDGFRα, STAT3, and K-RAS.

Keywords:

• DNA methylation
• extranodal natural killer/T-cell lymphoma
• miR-181c
• miR-34a
• miRNA

Acknowledgments

The authors would like to thank Yong-Goo Kim (Cancer Research Institute, Seoul National University, Seoul, Republic of Korea) for her technical assistance.

Disclosure statement

No potential conflicts of interest were disclosed by the authors.

Additional information

Funding

This research was supported by the Basic Science Research Program (grant No. NRF-2013R1A1A2013210 and NRF-2016R1D1A1B01015964) through the National Research Foundation (NRF) funded by the Ministry of Education, Science and Technology (MEST), Republic of Korea. Also funding was received from The Korean Society of Pathologists (Grant No. 2014–569), Republic of Korea.