Human microRNA-1245 down-regulates the NKG2D receptor in natural killer cells and impairs NKG2D-mediated functions

Abstract

We investigated the potential interactions between the 3'-untranslated region of the NKG2D gene and microRNA as well as their functional roles in the regulation of NKG2D expression and cytotoxicity in natural killer cells. ResultsTransforming growth factor-β1, a major negative regulator of NKG2D expression, post-transcriptionally up-regulated mature microRNA-1245 expression, thus down-regulating NKG2D expression and impairing NKG2D-mediated immune responses in natural killer cells. Conversely, microRNA-1245 down-regulation significantly increased the expression of NKG2D expression in natural killer cells, resulting in more efficient NKG2D-mediated cytotoxicity. ConclusionsThese results reveal a novel NKG2D regulatory pathway mediated by microRNA-1245, which may represent one of the mechanisms used by transforming growth factor-β1 to attenuate NKG2D expression in natural killer cells. © F e r r a t a S t o r t i F o u n d a t i o n © F e r r a t a S t o r t i F o u n d a t i o n

A functional polymorphism in the NKG2D gene modulates NK-cell cytotoxicity and is associated with susceptibility to Human Papilloma Virus-related cancers

“…The NK cell line YT, generously provided by Dr. K. Kasahara at the Department of Pediatrics of Kanazawa University11, and the chronic myeloid leukemia derived cell line OUN-1, kindly provided by Dr. M. Yasukawa from Ehime University in Japan, were cultured in RPMI 1640 + 10% FBS, 100 μg/ml streptomycin and 100 U/ml of penicillin12. The primary human lung embryonic fibroblasts (HELs), as previously described13, were cultured in DMEM supplemented with 5% newborn calf serum (NBCS) and 2 mM glutamine and used between passages 9–12.…”

“…The 3′ UTRs of the two individuals were nearly identical and differed only in the C or G nucleotide corresponding to the rs1049174 SNP, as confirmed by direct sequencing. PCR was performed with the premiers described previously11. These PCR products were then sub-cloned into pGL3 plasmid as described before11 to generate pGL3-NKG2D-3′UTR-HNK1 (C) and pGL3-NKG2D-3′UTR-LNK1 (G), designated thereafter as LNK-Luc and HNK-Luc, respectively.…”

“…PCR was performed with the premiers described previously11. These PCR products were then sub-cloned into pGL3 plasmid as described before11 to generate pGL3-NKG2D-3′UTR-HNK1 (C) and pGL3-NKG2D-3′UTR-LNK1 (G), designated thereafter as LNK-Luc and HNK-Luc, respectively. The 3′UTRs were inserted with the same orientation relative to each other, and the nucleotide sequences of the 3′UTRs of the plasmids were confirmed by DNA sequencing.…”

DNA demethylation and histone H3K9 acetylation determine the active transcription of the NKG2D gene in human CD8+T and NK cells

“…Here, we analyzed the distribution of found to downregulate NKG2D expression in NK cells, damping its cytotoxic function. 18 Human NKG2DL, MICA, MICB (MHC class I chainrelated A and B) and ULBPs 1-6 (UL-16 binding protein) are expressed at low levels in many normal tissues. 19,20 However, their expression is induced during genotoxic or cellular stress caused by infection or malignant transformation, alerting the immune system to adverse cellular conditions.…”

Regulation of Gene Expression by Exercise-Related Micrornas

“…These miRNAs are involved to several inflammatory processes commonly -181a), toll-like receptors (miR-132, let-7e), activation of NK cell receptor (miR-1245), and cytokine production (miR-146a) [122][123][124]. Physical exercise also modulates to the transcriptional regulation of key genes that could elucidate the mechanism of benefits on health by physical exercise on different immune cells, including neutrophils, macrophages, and lymphocytes [125][126][127][128][129].…”