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miR-24-3p Is Overexpressed in Hodgkin Lymphoma and Protects Hodgkin and Reed-Sternberg Cells from Apoptosis

Yuan, Y., Kluiver, J., Koerts, J., de Jong, D., Rutgers, B., Abdul Razak, F. R., Terpstra, M., Plaat, B., Nolte, I. M., Diepstra, A., Visser, L., Kok, K. & van den Berg, A., Jun-2017, In : The American Journal of Pathology. 187, 6, p. 1343-1355 13 p.

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  • miR-24-3p Is Overexpressed in Hodgkin Lymphoma and Protects Hodgkin and Reed-Sternberg Cells from Apoptosis

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DOI

miRNAs play important roles in biological processes, such as proliferation, metabolism, differentiation, and apoptosis, whereas altered expression levels contribute to diseases, such as cancers. We identified miRNAs with aberrant expression in Hodgkin lymphoma (HL) and investigated their role in pathogenesis. Small RNA sequencing revealed 84 significantly differentially expressed miRNAs in HL cell lines as compared to germinal center B cells. Three up-regulated miRNAs-miR-23a-3p, miR-24-3p, and miR-27a-3p-were derived from one primary miRNA transcript. Loss-of-function analyses for these miRNAs and their seed family members resulted in decreased growth on miR-24-3p inhibition in three HL cell lines and of miR-27a/b-3p inhibition in one HL cell line. Apoptosis analysis indicated that the effect of miR-24-3p on cell growth is at Least in part caused by an increase of apoptotic cells. Argonaute 2 immunoprecipitation revealed 1142 genes consistently targeted by miRNAs in at least three of four HL cell lines. Furthermore, 52 of the 1142 genes were predicted targets of miR-24-3p. Functional annotation analysis revealed a function related to cell growth, cell death, and/or apoptosis for 15 of the 52 genes. Western blotting of the top five genes showed increased protein levels on miR-24-3p inhibition for CDKN1B/P27(kiP1) and MYC, In summary, we showed that miR-24-3p is up-regulated in HL and its inhibition impairs cell growth possibly via targeting CDKN1B/P27(kiP1) and MYC.

Original languageEnglish
Pages (from-to)1343-1355
Number of pages13
JournalThe American Journal of Pathology
Volume187
Issue number6
Early online date20-Apr-2017
Publication statusPublished - Jun-2017

    Keywords

  • WORLD-HEALTH-ORGANIZATION, MYC-INDUCED APOPTOSIS, C-MYC, IN-VIVO, DOWN-REGULATION, CANCER-CELLS, EXPRESSION, MICRORNAS, INHIBITION, TARGET

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