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Glutamate receptor, ionotropic, kainate 5 (GRIK5) is a member of glutamate receptors participating, and the kainate receptor family has been proved to regulate cell proliferation and transformation. Our study aimed at exploring the role of GRIK5 in colon tumor progression. Three hundred and ninety eight colon cancer patients in The Cancer Genome Atlas Program (TCGA) data set and 26 clinical colon cancer patients were included for GRIK5 expression and prognosis analysis. GRIK5 overexpressed HCT116 and CT26 cell lines were established for cell proliferation and Transwell assay. Western blot analysis and immunostaining assay was conducted to evaluate the activation of activation of cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cell adhesion molecular 3 (CADM3) signaling in cell lines and tumor tissues. Subcutaneous CT26‐bearing mice model was established to examine GRIK5‐induced tumor growth and metastasis in vivo. Our study identified GRIK5 to be upregulated in patients with colon cancer, and higher GRIK5 levels correlated with the poor overall survival in patients. In vitro, GRIK5 overexpression markedly enhanced the proliferative properties and aggressive behaviors of colon cancer cells. Mechanistically, GRIK5 induced the activation of cAMP/PKA signaling, proceeded with augmented CADM3 expression, eventually resulting in sustained tumor growth. GRIK5 was a crucial scaffold in enabling colon cancer growth and metastasis, which offered a promising target for therapeutic manipulation of colon cancer. [ABSTRACT FROM AUTHOR]

Abstract Background Ultra-rare genetic variants, including non-recurrent copy number variations (CNVs) affecting important dosage-sensitive genes, are important contributors to the etiology of neurodevelopmental disorders (NDDs). Pairing family-based whole-genome sequencing (WGS) with detailed phenotype data can enable novel gene associations in NDDs. Methods We performed WGS of six members from a three-generation family, where three individuals each had a spectrum of features suggestive of a NDD. CNVs and sequence-level variants were identified and further investigated in disease and control databases. Results We identified a novel 252-kb deletion at 15q21 that overlaps the synaptic gene DMXL2 and the gene GLDN. The microdeletion segregated in NDD-affected individuals. Additional rare inherited and de novo sequence-level variants were found that may also be involved, including a missense change in GRIK5. Multiple CNVs and loss-of-function sequence variants affecting DMXL2 were discovered in additional unrelated individuals with a range of NDDs. Conclusions Disruption of DMXL2 may predispose to NDDs including autism spectrum disorder. The robust interpretation of private variants requires a multifaceted approach that incorporates multigenerational pedigrees and genome-wide and population-scale data.

Objective: To explore the effect of music in pain perception and the molecular mechanism. Methods: Mice were separated to control, music, music + inhibitor, and saline group. Percentage pain reduction of mice in each group was determined. The contents of 5-HT, Glu, and NE in cerebrospinal fluid of mice in the four groups were determined by HPLC. FISH was used to analyze the distribution characteristics of GRIK5 in hippocampal tissues. The protein expressions of GRIK5, NMDA 1, and TRPC1 in the hippocampal tissues were determined via western blot. Results : Mice exposed to music showed a higher percentage of pain reduction compared to model animals, while injection of GRIK5 inhibitor weakened the effect of music. It increased the contents of 5-HT, Glu, and NE in mouse models of depression. The fluorescence signal in music group was significantly stronger than saline group. Music remarkably increased the expression of GRIK5, DLG4, NMDA 1, and TRPC1 proteins when compared with saline group. Conclusion : Music promoted the secretion of Glu. The glutaminergic pathway sensed Glu, subsequently activated GRIK5, DLG4, and NMDA 1 proteins to excite dopaminergic neurons, and finally promoted the production of 5-HT.

Background: Ultra-rare genetic variants, including non-recurrent copy number variations (CNVs) affecting important dosage-sensitive genes, are important contributors to the etiology of neurodevelopmental disorders (NDDs). Pairing family-based whole-genome sequencing (WGS) with detailed phenotype data can enable novel gene associations in NDDs. Methods: We performed WGS of six members from a three-generation family, where three individuals each had a spectrum of features suggestive of a NDD. CNVs and sequence-level variants were identified and further investigated in disease and control databases. Results: We identified a novel 252-kb deletion at 15q21 that overlaps the synaptic gene DMXL2 and the gene GLDN. The microdeletion segregated in NDD-affected individuals. Additional rare inherited and de novo sequence-level variants were found that may also be involved, including a missense change in GRIK5. Multiple CNVs and loss-of-function sequence variants affecting DMXL2 were discovered in additional unrelated individuals with a range of NDDs. Conclusions: Disruption of DMXL2 may predispose to NDDs including autism spectrum disorder. The robust interpretation of private variants requires a multifaceted approach that incorporates multigenerational pedigrees and genome-wide and population-scale data. [ABSTRACT FROM AUTHOR]