The reciprocal interplay between TNFα and the circadian clock impacts on cell proliferation and migration in Hodgkin lymphoma cells

Mónica Abreu, Alireza Basti, Nikolai Genov, Gianluigi Mazzoccoli, Angela Relógio

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Abstract

A bidirectional interaction between the circadian network and effector mechanisms of immunity brings on a proper working of both systems. In the present study, we used Hodgkin lymphoma (HL) as an experimental model for a type of cancer involving cells of the immune system. We identified this cancer type among haematological malignancies has having a strong differential expression of core-clock elements. Taking advantage of bioinformatics analyses and experimental procedures carried out in III- and IV-stage HL cells, and lymphoblastoid B cells, we explored this interplay and bear out diverse interacting partners of both systems. In particular, we assembled a wide-ranging network of clock-immune-related genes and pinpointed TNF as a crucial intermediary player. A robust circadian clock hallmarked III-stage lymphoma cells, differently from IV-stage HL cells, which do not harbour a properly functioning clockwork. TNF and circadian gene modulation impacted on clock genes expression and triggered phenotypic changes in lymphoma cells, suggesting a crucial involvement of core-clock elements and TNF in the physiopathological mechanisms hastening malignancy. Our results move forward our understanding of the putative role of the core-clock and TNF in the pathobiology of Hodgkin lymphoma, and highlight their influence in cellular proliferation and migration in lymphatic cancers.

Original languageEnglish
Article number11474
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

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