Details

Autor(en) / Beteiligte

• Niu, Fubiao
• Dzikiewicz-Krawczyk, Agnieszka
• Koerts, Jasper
• de Jong, Debora
• Wijenberg, Laura
• Fernandez Hernandez, Margot
• Slezak-Prochazka, Izabella
• Winkle, Melanie
• Kooistra, Wierd
• van der Sluis, Tineke
• Rutgers, Bea
• Terpstra, Miente Martijn
• Kok, Klaas
• Kluiver, Joost
• van den Berg, Anke

Titel

MiR-378a-3p Is Critical for Burkitt Lymphoma Cell Growth

Ist Teil von

• Cancers, 2020-11, Vol.12 (12), p.3546

Ort / Verlag

Switzerland: MDPI AG

Erscheinungsjahr

2020

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• MicroRNAs (miRNAs) are small RNA molecules with important gene regulatory roles in normal and pathophysiological cellular processes. Burkitt lymphoma (BL) is an MYC-driven lymphoma of germinal center B (GC-B) cell origin. To gain further knowledge on the role of miRNAs in the pathogenesis of BL, we performed small RNA sequencing in BL cell lines and normal GC-B cells. This revealed 26 miRNAs with significantly different expression levels. For five miRNAs, the differential expression pattern was confirmed in primary BL tissues compared to GC-B cells. MiR-378a-3p was upregulated in BL, and its inhibition reduced the growth of multiple BL cell lines. RNA immunoprecipitation of Argonaute 2 followed by microarray analysis (Ago2-RIP-Chip) upon inhibition and ectopic overexpression of miR-378a-3p revealed 63 and 20 putative miR-378a-3p targets, respectively. Effective targeting by miR-378a-3p was confirmed by luciferase reporter assays for MAX Network Transcriptional Repressor (MNT), Forkhead Box P1 (FOXP1), Interleukin 1 Receptor Associated Kinase 4 (IRAK4), and lncRNA Just Proximal To XIST (JPX), and by Western blot for IRAK4 and MNT. Overexpression of IRAK4 and MNT phenocopied the effect of miR-378a-3p inhibition. In summary, we identified miR-378a-3p as a miRNA with an oncogenic role in BL and identified IRAK4 and MNT as miR-378a-3p target genes that are involved in its growth regulatory role.