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MX 2 is a novel regulator of cell cycle in melanoma cells
Author(s) -
Juraleviciute Marina,
Pozniak Joanna,
Nsengimana Jérémie,
Harland Mark,
RandersonMoor Juliette,
Wernhoff Patrik,
Bassarova Assia,
Øy Geir Frode,
Trøen Gunhild,
Flørenes Vivi Ann,
Bishop David Timothy,
Herlyn Meenhard,
NewtonBishop Julia,
Slipicevic Ana
Publication year - 2020
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12837
Subject(s) - melanoma , biology , cancer research , cell cycle , downregulation and upregulation , carcinogenesis , cell growth , cell culture , microphthalmia associated transcription factor , transcription factor , cell , gene , genetics
MX2 protein is a dynamin‐like GTPase2 that has recently been identified as an interferon‐induced restriction factor of HIV‐1 and other primate lentiviruses. A single nucleotide polymorphism (SNP), rs45430, in an intron of the MX2 gene, was previously reported as a novel melanoma susceptibility locus in genome‐wide association studies. Functionally, however, it is still unclear whether and how MX2 contributes to melanoma susceptibility and tumorigenesis. Here, we show that MX2 is differentially expressed in melanoma tumors and cell lines, with most metastatic cell lines showing lower MX2 expression than primary melanoma cell lines and melanocytes. Furthermore, high expression of MX2 RNA in primary melanoma tumors is associated with better patient survival. Overexpression of MX2 reduces in vivo proliferation partially through inhibition of AKT activation, suggesting that it can act as a tumor suppressor in melanoma. However, we have also identified a subset of melanoma cell lines with high endogenous MX2 expression where downregulation of MX2 leads to reduced proliferation. In these cells, MX2 downregulation interfered with DNA replication and cell cycle processes. Collectively, our data for the first time show that MX2 is functionally involved in the regulation of melanoma proliferation but that its function is context‐dependent.