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Last update 08 May 2025

SPRY2

Last update 08 May 2025

Basic Info

Synonyms

hSPRY2, Protein sprouty homolog 2, sprouty RTK signaling antagonist 2

+ [2]

Introduction

Antagonist of fibroblast growth factor (FGF) pathways via inhibition of FGF-mediated phosphorylation of ERK1/2 (By similarity). Thereby acts as an antagonist of FGF-induced retinal lens fiber differentiation, may inhibit limb bud outgrowth and may negatively modulate respiratory organogenesis (By similarity). Inhibits TGFB-induced epithelial-to-mesenchymal transition in retinal lens epithelial cells (By similarity). Inhibits CBL/C-CBL-mediated EGFR ubiquitination (PubMed:17974561).

Drugs associated with SPRY2

iRGD‐exo‐antagomiR‐BART1-5p

Target

SPRY2

Mechanism

SPRY2 inhibitors

Active Org.

University of Science & Technology of China

Originator Org.

University of Science & Technology of China

Active Indication

Nasopharyngeal Carcinoma

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with SPRY2

100 Translational Medicine associated with SPRY2

0 Patents (Medical) associated with SPRY2

396

Literatures (Medical) associated with SPRY2

01 Jul 2025·Journal of Clinical and Experimental Hepatology

Validation of Two Prognostic Gene Scores in Patients Undergoing Liver Resection for Hepatocellular Carcinoma

Article

Author: Schnabl, Stinna D ; O'Rourke, Colm J ; Andersen, Jesper B ; Kugler, Jan-Michael ; Dam Nielsen, Susanne ; Bull Nordkild, Sophie ; Pommergaard, Hans-Christian ; Klubien, Jeanett

Background/AimsSeveral prognostic gene signatures have been proposed as predictors of the prognosis of hepatocellular carcinoma (HCC), yet none are implemented in the clinical setting. We aimed to validate two gene scores previously derived from European cohorts.MethodsThe patients who underwent liver resection for HCC at Copenhagen University Hospital, Rigshospitalet from 2014 to 2018 were included. RNA sequencing determined the expression of genes in the '5-gene score' (HN1, RAN, RAMP3, KRT19, TAF9B) and 'HepatoPredict' (CLU, DPT, SPRY2, CAPSN1). Univariable Cox regression assessed associations with overall and disease-free survival. These parameters were also analyzed in the The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) (n = 359) and National Institute of Health (NIH) (n = 178) cohorts.ResultsAmong 51 patients (88% male), 59% had no underlying liver disease and 25% had cirrhosis. No individual genes were significantly associated with overall survival in the Danish cohort. In the TCGA-LIHC cohort, CLU was linked to better overall survival, and in the NIH cohort, high expression of SPRY2 was associated with poorer overall survival. In the TCGA-LIHC cohort, HN1, RAN, and TAF9B were associated with poorer overall survival, while RAMP3 was linked to better overall survival. No genes were associated with disease-free survival.ConclusionFew individual genes significantly predicted survival in the larger cohorts, and none in the Danish cohort. However, the clinical implication of this needs further investigation.

01 Jan 2025·Cancer Medicine

Assessing the Causal Effect of Circulating Protein‐To‐Protein Ratio on the Risk of Morbidity of Hepatocellular Carcinoma

Article

Author: Zhang, Mingwei ; Wan, Xiaoye ; Yue, Qiuyuan ; Xu, Shaohua ; Lin, Xi ; Li, Xiaoxia ; Li, Yueming

ABSTRACTObjectiveSeveral observational studies have identified an association between plasma proteins and hepatocellular carcinoma (HCC). This study aimed to explore the potential causal relationship between the circulating protein‐to‐protein ratio and the morbidity risk of HCC.MethodsGenetic association data for circulating plasma proteins and 2821 protein‐to‐protein ratios were sourced from the UKB PPP and Suhre's study. Genetic association data for HCC were sourced from the FinnGen cohort (finngen‐R11‐HCC) and the IEU OpenGWAS project (ieu‐b‐4953). Subsequently, a two‐sample Mendelian randomization (MR) and drug‐targeted MR approach were used to evaluate causality associations. To bolster the robustness of our findings, we conducted a series of sensitivity analyses.ResultsEight protein–protein pairs were identified as causal factors for HCC in the two independent cohorts. For each standard deviation increase in protein–protein pair expression, susceptibility to HCC fluctuated from 0.4974 (95% confidence interval [CI]: 0.2506–0.9871) for the LAT2/SPRY2 protein pair to 1.9763 (95% CI: 1.3009–3.0026) for the ERBIN/LAT2 protein pair. However, among the significant protein pairs, only one circulating protein, TDRKH (odds ratio: 0.5964, 95% CI: 0.4196–0.8476), was causally associated with HCC.ConclusionUsing multiple datasets and methods, eight protein–protein pairs were identified as having causal associations with HCC. Protein–protein interactions can provide meaningful findings beyond simple pQTL analysis.

02 Dec 2024·Journal of Crohn's and Colitis

MSCs-exosomes Can Promote Macrophage M2 Polarisation via Exosomal miR-21-5p through Mesenteric Injection: A Promising Way to Attenuate Murine Colitis

Article

Author: Shen, Chen ; Li, Yi ; Zhou, Yudi ; Zhang, Yi ; Chen, Hong ; Qian, Wenwei ; Wang, Jin ; Wu, Enhao ; Bai, Yanjin ; Wang, Sheng ; Yao, Jun

AbstractBackground and AimsExosome-based therapies are gaining increasing attention, with growing evidence suggesting a link between alterations in mesentery adipose tissue [MAT] and intestinal disease in Crohn’s disease [CD]. However, the specific mechanism by which mesenchymal stem cells [MSCs]-Exos may alleviate colitis through targeting MAT remains not fully understood.MethodsHuman umbilical cord MSCs [HucMSCs] were cultured to isolate the corresponding exosomes [HucMSCs-Exos], which were confirmed by their morphology, size distribution, and expression of markers. In vivo, 2,4,6-trinitrobenzenesulphonic acid [TNBS]- and dextran sodium sulphate [DSS]-induced mouse colitis models were used to detect the therapeutic effects of HucMSCs-Exos. Enzyme-linked immunosorbent assay [ELISA], quantitative reverse transcription-polymerase chain reaction [qRT-PCR], western blotting, and immunofluorescence determined the expression of key molecules. Luciferase reporter assay was used to confirm the relationship between miR-21-5p and SPRY2.ResultsExosomes treatment through mesenteric injection demonstrated therapeutic effects on mesenteric inflammation and colitis. These therapeutic benefits were contingent on macrophages, significantly facilitating the M2 polarisation of mesenteric macrophages. The expression data from GSE159814 and GSE211008 revealed that exosomal miR-21-5p was enriched in HucMSCs-Exos and could be delivered to macrophages. Additionally, the results indicated that miR-21-5p could directly target the 3’UTR of SPRY2 and activate the phosphorylation of ERK to modify macrophage phenotypes. Mechanistically, exosomal miR-21-5p derived from HucMSCs could promote macrophage M2 polarisation via the SPRY2/ERK axis.ConclusionMesenteric injection of HucMSCs-Exos significantly alleviates mesenteric inflammation and colitis by promoting mesenteric macrophage M2 polarisation, making it a promising approach to treat colitis and suggesting therapeutic potential role of exosomal miR-21-5p in CD.

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