Innate immune sensor laboratory of genetics and physiology 2 suppresses tumor cell growth and functions as a prognostic marker in neuroblastoma

摘要

The innate immune receptors, such as toll‐like receptor 3 (TLR3), melanoma differentiation‐associated 5 (MDA5) and retinoic acid‐inducible gene‐I (RIG‐I), have been shown to be differentially expressed in neuroblastoma (NB) and promote dsRNA poly (I:C)‐induced NB suppression in vitro and in vivo. However, the role of another important innate immune cytosolic sensor, laboratory of genetics and physiology 2 (LGP2), in the cancer behavior of NB remains unclear. Here, we demonstrated that the expression levels of LGP2 were either low or undetectable in all NB cell lines tested with or without MYCN amplification. LGP2 expression levels were significantly increased only in NB cells without MYCN amplification, including SK‐N‐AS and style="fixed-case">SK‐N‐ style="fixed-case">FI after poly (I:C) treatment in vitro and in mouse xenograft models. Ectopic expression of style="fixed-case">LGP2 in style="fixed-case">NB cells significantly enhanced poly (I:C)‐induced style="fixed-case">NB cell death associated with downregulation of style="fixed-case">MDA5, style="fixed-case">RIG‐I, style="fixed-case">MAVS and Bcl‐2, as well as upregulation of Noxa and style="fixed-case">tBid. By immunofluorescence analyses, style="fixed-case">LGP2 localized mainly in the cytoplasm of style="fixed-case">NB cells after poly (I:C) treatment. In human style="fixed-case">NB tissue samples, cytoplasmic style="fixed-case">LGP2 expression was positively correlated with histological differentiation and inversely correlated with style="fixed-case">MYCN amplification. Positive cytoplasmic style="fixed-case">LGP2 expression in tumor tissues could predict a favorable outcome in style="fixed-case">NB patients independent of other prognostic factors. In short, style="fixed-case">LGP2 was effective in promoting poly (I:C)‐induced style="fixed-case">NB suppression and cytoplasmic style="fixed-case">LGP2 can serve as an independent favorable prognostic factor in style="fixed-case">NB patients.