Rspo2

BACKGROUND: Esophageal cancer is a highly aggressive malignancy with limited treatment options and poor prognosis. The identification of novel molecular subtypes and therapeutic targets is crucial for improving clinical outcomes. METHOD: In this study, we investigated the role of R-spondin 2 (RSPO2) in esophageal cancer and its association with mitochondrial metabolism. Using bioinformatics analysis of publicly available datasets, we identified a panel of RSPO2-related mitochondrial metabolism genes and their expression patterns in esophageal cancer...

RSPO2 protein may provide valuable insights into the mechanism underlying various types of tumorigenesis. The role of RSPO2 in pan-cancer has not been reported so far. Therefore, this study aimed to provide a comprehensive analysis of RSPO2 from a pan-cancer perspective employing multiomics data. The expression profile and function of RSPO2 across different tumors were investigated using various web-based tools UALCAN, GEPIA, TIMER, Human Protein Atlas, cBioPortal, TISIDB, STRING, and Metascape to interpret the expression profile, promoter methylation status, genomic alterations, survival analysis, protein-protein interaction, correlation with immune cell subtypes, tumor immune microenvironment and enrichment analysis...

Heterotopic ossification (HO) is a pathological process in which ectopic bone develops in soft tissues within the skeletal system. Endochondral ossification can be divided into the following types of acquired and inherited ossification: traumatic HO (tHO) and fibrodysplasia ossificans progressiva (FOP). Nuclear transcription factor kappa B (NF-κB) signalling is essential during HO. NF-κB signalling can drive initial inflammation through interactions with the NOD-like receptor protein 3 (NLRP3) inflammasome, Sirtuin 1 (SIRT1) and AMP-activated protein kinase (AMPK)...

Establishment of the left-right (LR, sinistral, dextral) body axis in many vertebrate embryos relies on cilia-driven leftward fluid flow within an LR organizer (LRO). A cardinal question is how leftward flow triggers symmetry breakage. The chemosensation model posits that ciliary flow enriches a signaling molecule on the left side of the LRO that promotes sinistral cell fate. However, the nature of this sinistralizing signal has remained elusive. In the Xenopus LRO, we identified the stem cell growth factor R-Spondin 2 (Rspo2) as a symmetrically expressed, sinistralizing signal...

Signal transduction at the neuromuscular junction (NMJ) is compromised in a diverse array of diseases including congenital myasthenic syndromes (CMS). Germline mutations in CHRNE encoding the acetylcholine receptor (AChR) ε subunit are the most common cause of CMS. An active form of vitamin D, calcitriol, binds to vitamin D receptor (VDR) and regulates gene expressions. We found that calcitriol enhanced MuSK phosphorylation, AChR clustering, and myotube twitching in co-cultured C2C12 myotubes and NSC34 motor neurons...

In substance use disorders, drug use as unconditioned stimulus (US) reinforces drug taking. Meanwhile, drug-associated cues (conditioned stimulus [CS]) also gain incentive salience to promote drug seeking. The basolateral amygdala (BLA) is implicated in both US- and CS-mediated responses. Here, we show that two genetically distinct BLA neuronal types, expressing Rspo2 versus Ppp1r1b, respectively, project to the nucleus accumbens (NAc) and form monosynaptic connections with both dopamine D1 and D2 receptor-expressing neurons...

BACKGROUND: The aggressive phenotype of fibroblast-like synoviocytes (FLS) has been identified as a contributing factor to the exacerbation of rheumatoid arthritis (RA) through the promotion of synovitis and cartilage damage. Regrettably, there is currently no effective therapeutic intervention available to address this issue. Recent research has shed light on the crucial regulatory role of R-spondin-2 (Rspo2) in cellular proliferation, cartilage degradation, and tumorigenesis. However, the specific impact of Rspo2 on RA remains poorly understood...

OBJECTIVE: This study aimed to explore the specific function of M2 macrophages in intervertebral disc degeneration (IDD). METHODS: Intervertebral disc (IVD) samples from normal (n=4) and IDD (n=6) patients were collected, and the expression of M2-polarized macrophage marker, CD206, was investigated using immunohistochemical staining. Nucleus pulposus cells (NPCs) in a TNF-α environment were obtained, and a mouse caudal IVD puncture model was established. Mice with Rheb deletions, specifically in the myeloid lineage, were generated and subjected to surgery-induced IDD...

The significant morphological differences and abundant germplasm resources of Chinese indigenous dog breeds can be attributed to the diverse geographical environment, including plateaus, mountains, and a long history of raising dogs. The combination of both natural and artificial selection during the past several thousand years has led to hundreds of dog breeds with distinct morphological traits and environmental adaptations. China is one of the earliest countries to domesticate dogs and there are more than 50 ancient indigenous dog breeds...

R-spondins are secretory proteins localized in the endoplasmic reticulum and Golgi bodies and are processed through the secretory pathway. Among the R-spondin family, RSPO2 has emanated as a novel regulator of Wnt signaling, which has now been acknowledged in numerous in vitro and in vivo studies. Cancer is an abnormal growth of cells that proliferates and spreads uncontrollably due to the accumulation of genetic and epigenetic factors that constitutively activate Wnt signaling in various types of cancer. Colorectal cancer (CRC) begins when cells in the colon and rectum follow an indefinite pattern of division due to aberrant Wnt activation as one of the key hallmarks...

BACKGROUND: Promoter hypermethylation of tumour suppressor genes is frequently observed during the malignant transformation of colorectal cancer (CRC). However, whether this epigenetic mechanism is functional in cancer or is a mere consequence of the carcinogenic process remains to be elucidated. RESULTS: In this work, we performed an integrative multi-omic approach to identify gene candidates with strong correlations between DNA methylation and gene expression in human CRC samples and a set of 8 colon cancer cell lines...

Shepherd and hunting dogs have undergone divergent selection for specific tasks, resulting in distinct phenotypic and behavioural differences. Italy is home to numerous recognized and unrecognized breeds of both types, providing an opportunity to compare them genomically. In this study, we analysed SNP data obtained from the CanineHD BeadChip, encompassing 116 hunting dogs (representing 6 breeds) and 158 shepherd dogs (representing 9 breeds). We explored the population structure, genomic background, and phylogenetic relationships among the breeds...

The Chinese soft-shelled turtle, Pelodiscus sinensis , is an important aquaculture species in China that exhibits distinct sexual dimorphism; male individuals are economically more valuable than females. In vertebrates, several R-spondin family proteins have been associated with sex differentiation mechanisms; however, their involvement in P. sinensis sex differentiation is unclear. Exogenous hormones such as estradiol (E2) also influence the sex differentiation of P. sinensis and induce sexual reversal. In the present study, we investigated the effects of E2 on the embryonic development of P...

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LGR4 and LGR5 are two homologous receptors that potentiate Wnt/β-catenin signaling in response to R-spondin (RSPO) ligands. The RSPO and LGR4 complex binds to and inhibits activities of two related E3 ubiquitin ligases, RNF43 and ZNRF3, and thus protects Wnt receptors from the E3 ligase-mediated degradation. The RSPO and LGR5 complex, however, does not interact with the E3 ligases, and the structural basis of this difference remained unknown. Here we examined the affinities of monovalent and bivalent RSPO ligands in binding to LGR4, RNF43/ZNRF3, and LGR5 in whole cells and found unique features among the receptors and E3 ligases...

Chondrocyte degeneration and classically activated macrophage (AM)-related inflammation play critical roles in osteoarthritis (OA). Here, we explored the effects of astaxanthin and Rspo2 on OA in vitro and in vivo . We observed that the Rspo2 gene was markedly elevated in synovial tissues of OA patients compared with healthy controls. In 2D cultures, Rspo2 and inflammatory factors were enhanced in AMs compared with nonactivated macrophages (NMs), and the protein expression levels of Rspo2, β-catenin, and inflammatory factors were increased, and anabolic markers were reduced in osteoarthritic chondrocytes (OACs) compared to normal chondrocytes (NCs)...

Proteolysis-targeting chimeras (PROTACs) are an emerging technology for therapeutic intervention, but options to target cell surface proteins and receptors remain limited. Here we introduce ROTACs, bispecific WNT- and BMP-signaling-disabled R-spondin (RSPO) chimeras, which leverage the specificity of these stem cell growth factors for ZNRF3/RNF43 E3 transmembrane ligases, to target degradation of transmembrane proteins. As a proof-of-concept, we targeted the immune checkpoint protein, programmed death ligand 1 (PD-L1), a prominent cancer therapeutic target, with a bispecific RSPO2 chimera, R2PD1...

BACKGROUND: The clinical significance of fusion genes in colorectal cancer remains unclear. The purpose of this study was to determine the incidence of fusion genes in colorectal cancer and explore their clinical significance by screening for common fusion genes in a large Japanese cohort. METHODS: This study involved 1588 patients. The incidence of 491 fusion genes was examined using a designed fusion panel. In addition, the patients were classified into two groups (RSPO fusion-positive or -negative) according to the presence of RSPO fusions, and the clinicopathological and genetic characteristics of both groups were compared...

PURPOSE: Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Leucine-rich repeat containing G-protein-coupled receptors 4 (LGR4) participates in tumor progression, invasion, and metastasis. Our study aimed to investigate the effect of LGR4 with epidermal growth factor receptor (EGFR) in HCC cells. METHODS: We employed Hep3B and Huh7 cells to conduct our research. Comprehensive biological activities were characterized by CCK8 and transwell assay...

We performed transcriptome analysis using RNA sequencing on substantia nigra pars compacta (SNpc) from mice after acute and chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment and from Parkinson's disease (PD) patients. Acute and chronic exposure to MPTP resulted in decreased expression of genes involved in sodium channel regulation. However, upregulation of pro-inflammatory pathways was seen after single dose but not after chronic MPTP treatment. Dopamine biosynthesis and synaptic vesicle recycling pathways were downregulated in PD patients and after chronic MPTP treatment in mice...