Gene Symbol: SPRY4
Description: sprouty RTK signaling antagonist 4
Alias: HH17, protein sprouty homolog 4, sprouty homolog 4
Species: human
Products:     SPRY4

Top Publications

  1. Khaitan D, Dinger M, Mazar J, Crawford J, Smith M, Mattick J, et al. The melanoma-upregulated long noncoding RNA SPRY4-IT1 modulates apoptosis and invasion. Cancer Res. 2011;71:3852-62 pubmed publisher
    ..One of these lncRNAs, SPRY4-IT1 (GenBank accession ID AK024556), is derived from an intron of the SPRY4 gene and is predicted to contain ..
  2. Lao D, Chandramouli S, Yusoff P, Fong C, Saw T, Tai L, et al. A Src homology 3-binding sequence on the C terminus of Sprouty2 is necessary for inhibition of the Ras/ERK pathway downstream of fibroblast growth factor receptor stimulation. J Biol Chem. 2006;281:29993-30000 pubmed
    ..Spry2 is considerably more inhibitory than Spry1 or Spry4, and this correlates with the binding to Grb2 via a C-terminal proline-rich sequence that is found exclusively on ..
  3. Turnbull C, Rapley E, Seal S, Pernet D, Renwick A, Hughes D, et al. Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer. Nat Genet. 2010;42:604-7 pubmed publisher
    ..Finally, we identified a locus on chromosome 9 (rs755383, OR=1.37, P=1.12x10(-23)), containing the sex determination gene DMRT1, which has been linked to teratoma susceptibility in mice. ..
  4. Rapley E, Turnbull C, Al Olama A, Dermitzakis E, Linger R, Huddart R, et al. A genome-wide association study of testicular germ cell tumor. Nat Genet. 2009;41:807-10 pubmed publisher
    ..05-3.19), P = 10(-31)). KITLG, encoding the ligand for the receptor tyrosine kinase KIT, which has previously been implicated in the pathogenesis of TGCT and the biology of germ cells, may explain the association on chromosome 12. ..
  5. Kanetsky P, Mitra N, Vardhanabhuti S, Li M, Vaughn D, Letrero R, et al. Common variation in KITLG and at 5q31.3 predisposes to testicular germ cell cancer. Nat Genet. 2009;41:811-5 pubmed publisher
    ..07, 95% CI = 2.29-4.13, respectively). We found associations with rs4324715 and rs6897876 at 5q31.3 near SPRY4 (sprouty 4; P < 5.0 x 10(-6) in discovery)...
  6. Park S, Arai Y, Kim B, Bello A, Ashraf S, Park H, et al. SPRY4 suppression facilitates osteogenic differentiation in adipose-derived mesenchymal stem cells. Tissue Eng Part A. 2019;: pubmed publisher
    ..Although the role of some SPRY isoforms in MSC differentiation is known, the function SPRY4 isoform has not been fully elucidated...
  7. Zhang C, Wang H, Liu X, Hu Y, Ding L, Zhang X, et al. Oncogenic microRNA-411 promotes lung carcinogenesis by directly targeting suppressor genes SPRY4 and TXNIP. Oncogene. 2019;38:1892-1904 pubmed publisher
    ..Mechanically, SPRY4 is confirmed a direct target of miR-411-5p/3p...
  8. Wang Y, He H, Liyanarachchi S, Genutis L, Li W, Yu L, et al. The role of SMAD3 in the genetic predisposition to papillary thyroid carcinoma. Genet Med. 2018;20:927-935 pubmed publisher
    ..of SMAD3 in thyroid cancer cell lines revealed its regulatory gene network including two upregulated genes, SPRY4 and SPRY4-IT1...
  9. Kumar R, Njauw C, Reddy B, Ji Z, Rajadurai A, Klebanov N, et al. Growth suppression by dual BRAF(V600E) and NRAS(Q61) oncogene expression is mediated by SPRY4 in melanoma. Oncogene. 2019;: pubmed publisher
    ..Through differential gene expression analysis, we identified SPRY4 as the potential mediator of this synthetic response to dual oncogene suppression...

More Information

Publications126 found, 100 shown here

  1. Zhang H, Yang F, Yan Y, Che J, Zheng J. High expression of long non-coding RNA SPRY4-IT1 predicts poor prognosis of clear cell renal cell carcinoma. Int J Clin Exp Pathol. 2014;7:5801-9 pubmed
    ..lncRNAs SPRY4-IT1 has recently been identified to be involved in tumorigenesis of several cancers such as non-small cell lung ..
  2. Lochovska K, Peterkova R, Pavlikova Z, Hovorakova M. Sprouty gene dosage influences temporal-spatial dynamics of primary enamel knot formation. BMC Dev Biol. 2015;15:21 pubmed publisher
    ..Using mouse embryos with different dosages of Spry2 and Spry4 genes, we showed that during the normal development of M1 in the mandible the sooner appearing Shh signaling ..
  3. Kratz C, Greene M, Bratslavsky G, Shi J. A stratified genetic risk assessment for testicular cancer. Int J Androl. 2011;34:e98-102 pubmed publisher
    ..genome-wide association studies of testicular cancer have uncovered predisposition alleles in or near KITLG, BAK1, SPRY4, TERT, ATF7IP and DMRT1...
  4. Xiao L, Rao J, Cao S, Liu L, Chung H, Zhang Y, et al. Long noncoding RNA SPRY4-IT1 regulates intestinal epithelial barrier function by modulating the expression levels of tight junction proteins. Mol Biol Cell. 2016;27:617-26 pubmed publisher
    ..Here we show that the lncRNA SPRY4-IT1 regulates the intestinal epithelial barrier function by altering expression of tight junction (TJ) proteins...
  5. Zhan Y, Du L, Wang L, Jiang X, Zhang S, Li J, et al. Expression signatures of exosomal long non-coding RNAs in urine serve as novel non-invasive biomarkers for diagnosis and recurrence prediction of bladder cancer. Mol Cancer. 2018;17:142 pubmed publisher
    ..A panel consisting of three differently expressed lncRNAs (MALAT1, PCAT-1 and SPRY4-IT1) was established for BC diagnosis in the training set, showing an area under the receiver-operating ..
  6. Zuo Q, Huang S, Zou Y, Xu Y, Jiang Z, Zou S, et al. The Lnc RNA SPRY4-IT1 Modulates Trophoblast Cell Invasion and Migration by Affecting the Epithelial-Mesenchymal Transition. Sci Rep. 2016;6:37183 pubmed publisher
    ..The long noncoding RNA SPRY4-IT1 is more highly expressed in preeclamptic human placentas than in normal placentas...
  7. Cai Y, Zhang S, Zhang Y, Pan X, Feng K, Chen L, et al. Identification of the Gene Expression Rules That Define the Subtypes in Glioma. J Clin Med. 2018;7: pubmed publisher
    ..such as IGFBP2, IGF2BP3, PRDX1, NOV, NEFL, HOXA10, GNG12, SPRY4, and BCL11A, were identified...
  8. Kratz C, Bratslavsky G, Shi J. The clinical utility of testicular cancer risk loci. Genome Med. 2011;3:1 pubmed publisher
    ..testicular germ cell tumors have uncovered predisposition alleles in or near several genes, including KITLG, BAK1, SPRY4, TERT, ATF7IP, and DMRT1...
  9. Li H, Liu C, Lu Z, Chen L, Wang J, Li Y, et al. Upregulation of the long non-coding RNA SPRY4-IT1 indicates a poor prognosis and promotes tumorigenesis in ovarian cancer. Biomed Pharmacother. 2017;88:529-534 pubmed publisher
    ..LncRNA SPRY4-IT1 serves as a novel prognostic biomarker for hepatocellular carcinoma...
  10. Zahir F, Mwenifumbo J, Chun H, Lim E, van Karnebeek C, Couse M, et al. Comprehensive whole genome sequence analyses yields novel genetic and structural insights for Intellectual Disability. BMC Genomics. 2017;18:403 pubmed publisher
    ..115_116delinsTA and UPF1 c.1576_1577delinsA, and de novo SNVs in CACNB3 c.1289G?>?A, and SPRY4 c.508 T?>?A, of uncertain significance...
  11. Lee B, Mazar J, Aftab M, Qi F, Shelley J, Li J, et al. Long noncoding RNAs as putative biomarkers for prostate cancer detection. J Mol Diagn. 2014;16:615-26 pubmed
    ..AK024556 (SPRY4-IT1) was highly up-regulated in human prostate cancer cell line PC3 but not in LNCaP, and siRNA knockdown of SPRY4-..
  12. Alves Ferreira M, Pinho T, Sousa A, Sequeiros J, Lemos C, Alonso I. A novel SPRY2 and SPRY4 interaction increases tooth agenesis susceptibility. Bull Group Int Rech Sci Stomatol Odontol. 2012;51:e17 pubmed
    ..Short Communication selected from the Oral Presentations of the 56th Congress of the Groupèment International pour la Recherche Scientifique en Stomatologie et Odontologie, Peñafiel (Portugal) May 2012. ..
  13. Wu H, Wang Y, Chen T, Li Y, Wang H, Zhang L, et al. The N-terminal polypeptide derived from vMIP-II exerts its anti-tumor activity in human breast cancer by regulating lncRNA SPRY4-IT1. Biosci Rep. 2018;38: pubmed publisher
    Accumulating evidence demonstrates that long non-coding RNA (lncRNA) sprouty4-intron transcript 1 (lncRNA SPRY4-IT1) plays a vital role in the development of breast cancer...
  14. Thiele J, Hosek P, Kralovcova E, Ostasov P, Liska V, Bruha J, et al. lncRNAs in Non-Malignant Tissue Have Prognostic Value in Colorectal Cancer. Int J Mol Sci. 2018;19: pubmed publisher
    ..i>CCAT1, GAS5, linc-ROR, MALAT1, MIR155HG, PCAT1, SPRY4-IT1 and TUG1...
  15. Zhao Z, Chen C, Rillahan C, Shen R, Kitzing T, McNerney M, et al. Cooperative loss of RAS feedback regulation drives myeloid leukemogenesis. Nat Genet. 2015;47:539-43 pubmed publisher
    ..cells harboring a Kras(G12D) allele retained low levels of Ras signaling owing to negative feedback involving Spry4 that prevented transformation...
  16. Tong Y, Wang X, Zhou X, Liu Z, Yang T, Shi W, et al. Identification of the long non-coding RNA POU3F3 in plasma as a novel biomarker for diagnosis of esophageal squamous cell carcinoma. Mol Cancer. 2015;14:3 pubmed publisher
    ..Ten lncRNAs (HOTAIR, AFAP1-AS1, POU3F3, HNF1A-AS1, 91H, PlncRNA1, SPRY4-IT1, ENST00000435885.1, XLOC_013104 and ENST00000547963...
  17. Hua K, Wang M, Chen M, Wei L, Chen C, Ko C, et al. The H3K9 methyltransferase G9a is a marker of aggressive ovarian cancer that promotes peritoneal metastasis. Mol Cancer. 2014;13:189 pubmed publisher
    ..quantitative RT-PCR analysis revealed that G9a regulates a cohort of tumor suppressor genes including CDH1, DUSP5, SPRY4, and PPP1R15A in ovarian cancer...
  18. Das M, Furu K, Evensen H, Haugen Ø, Haugen T. Knockdown of SPRY4 and SPRY4-IT1 inhibits cell growth and phosphorylation of Akt in human testicular germ cell tumours. Sci Rep. 2018;8:2462 pubmed publisher
    ..association studies have so far identified about 50 susceptibility loci associated with TGCT, including SPRY4. SPRY4 has shown tumour suppressor activity in several cancer cells, such as lung and prostate, while it was found ..
  19. Guo W, Zhong K, Wei H, Nie C, Yuan Z. Long non-coding RNA SPRY4-IT1 promotes cell proliferation and invasion by regulation of Cdc20 in pancreatic cancer cells. PLoS ONE. 2018;13:e0193483 pubmed publisher
    ..Long non-coding RNA SPRY4-IT1 (sprouty4-intron transcript 1) has been reported to play an oncogenic role in various types of human ..
  20. Plotnik J, Budka J, Ferris M, Hollenhorst P. ETS1 is a genome-wide effector of RAS/ERK signaling in epithelial cells. Nucleic Acids Res. 2014;42:11928-40 pubmed publisher
    ..genes, but also identified a surprising role for ETS1 in the repression of genes such as DUSP4, DUSP6 and SPRY4 that provide negative feedback to the RAS/ERK pathway...
  21. Zhou Y, Wang D, Pang Q. Long noncoding RNA SPRY4-IT1 is a prognostic factor for poor overall survival and has an oncogenic role in glioma. Eur Rev Med Pharmacol Sci. 2016;20:3035-9 pubmed
    ..The purpose of this study is to investigate the clinical significance of lncRNA SPRY4-IT1 in glioma...
  22. Gao S, Zhao Z, Wu R, Zhang Y, Zhang Z. Prognostic value of long noncoding RNAs in gastric cancer: a meta-analysis. Onco Targets Ther. 2018;11:4877-4891 pubmed publisher
    ..of CDKN1A antisense DNA damage activated RNA [PANDAR], Pvt1 oncogene [PVT1], SOX2 overlapping transcript [Sox2ot], SPRY4 intronic transcript 1 [SPRY4-IT1], urothelial cancer associated 1 [UCA1], X inactive specific transcript [XIST], ..
  23. Goldshmit Y, Frisca F, Kaslin J, Pinto A, Tang J, Pébay A, et al. Decreased anti-regenerative effects after spinal cord injury in spry4-/- mice. Neuroscience. 2015;287:104-12 pubmed publisher
    ..2012, 2014). One of the downstream signaling target genes of Fgf is spry4, which acts as a feedback inhibitor for Fgf signaling...
  24. Hu X, Bao J, Wang Z, Zhang Z, Gu P, Tao F, et al. The plasma lncRNA acting as fingerprint in non-small-cell lung cancer. Tumour Biol. 2016;37:3497-504 pubmed publisher
    ..The candidate lncRNAs were validated by qRT-PCR arranged in the training and validation sets. Circulating SPRY4-IT1, ANRIL, and NEAT1 were significantly increased in plasma samples of NSCLC patients during training set and ..
  25. Thongrong S, Hausott B, Marvaldi L, Agostinho A, Zangrandi L, Burtscher J, et al. Sprouty2 and -4 hypomorphism promotes neuronal survival and astrocytosis in a mouse model of kainic acid induced neuronal damage. Hippocampus. 2016;26:658-67 pubmed publisher
    ..Among the four Sprouty isoforms, Spry2 and Spry4 are expressed in the hippocampus...
  26. Liu Y, Chen W, Kung W, Huang H. Plant miRNAs found in human circulating system provide evidences of cross kingdom RNAi. BMC Genomics. 2017;18:112 pubmed publisher
    ..seed sequences as hsa-miR-4259 and hsa-miR-4715-5p, was predicted to target human JAK-STAT signaling pathway gene SPRY4 and transcription regulation genes...
  27. Peng W, Wu G, Fan H, Wu J, Feng J. Long noncoding RNA SPRY4-IT1 predicts poor patient prognosis and promotes tumorigenesis in gastric cancer. Tumour Biol. 2015;36:6751-8 pubmed publisher
    ..However, investigation of lncRNAs on GC is still in its infancy. In this study, we focused on lncRNA SPRY4 intronic transcript 1 (SPRY4-IT1) and investigated its expression pattern, clinical significance, biological ..
  28. So W, Cheng J, Fan Q, Wong A, Huntsman D, Gilks C, et al. Loss of Sprouty2 in human high-grade serous ovarian carcinomas promotes EGF-induced E-cadherin down-regulation and cell invasion. FEBS Lett. 2015;589:302-9 pubmed publisher
    ..Oligonucleotide (HEEBO) microarray results showed that the mRNA levels of SPRY2, but not of SPRY1 or SPRY4, are down-regulated in high-grade serous ovarian carcinoma (HGSC) tissues and epithelial ovarian cancer (EOC) cell ..
  29. Yang L, Cheng X, Ge N, Guo W, Feng F, Wan F. Long non-coding RNA SPRY4-IT1 promotes gallbladder carcinoma progression. Oncotarget. 2017;8:3104-3110 pubmed publisher
    ..Long non-coding RNAs (lncRNAs) are found to be dysregulated in a variety of cancers, including GBC. SPRY4-IT1 has been recently revealed as oncogenic regulator in many cancers...
  30. Xu J, Ding R, Xu Y. Effects of long non-coding RNA SPRY4-IT1 on osteosarcoma cell biological behavior. Am J Transl Res. 2016;8:5330-5337 pubmed
    ..b>SPRY4-IT1 has been recently revealed as oncogenic regulator in various cancers, while its clinical value and potential ..
  31. Nie Z, Wang Y, Mei Y, Lin X, Zhang G, Sun H, et al. Prognostic significance of long noncoding RNA Z38 as a candidate biomarker in breast cancer. J Clin Lab Anal. 2018;32: pubmed publisher
    ..The expression levels of SPRY4-IT1 in 110 self-paired specimens of breast cancer and adjacent normal breast tissues were measured by quantitative ..
  32. Sun M, Huang F, Yu D, Zhang Y, Xu H, Zhang L, et al. Autoregulatory loop between TGF-β1/miR-411-5p/SPRY4 and MAPK pathway in rhabdomyosarcoma modulates proliferation and differentiation. Cell Death Dis. 2015;6:e1859 pubmed publisher
    ..a luciferase reporting system and sequence analysis, the potential target of miR-411-5p was identified as sprouty homolog 4 (SPRY4), which inhibits protein kinase Cα-mediated activation of mitogen-activated protein kinases (MAPKs)..
  33. Brinkhof B, van Tol H, Groot Koerkamp M, Riemers F, IJzer S, Mashayekhi K, et al. A mRNA landscape of bovine embryos after standard and MAPK-inhibited culture conditions: a comparative analysis. BMC Genomics. 2015;16:277 pubmed publisher
    ..Expression of other genes in the MAPK pathway including DUSP4 and SPRY4, or influenced by MAPK inhibition such as IFNT, was down-regulated...
  34. Thys A, Vandenberghe P, Hague P, Klein O, Erneux C, Vanderwinden J. Hyperplasia of interstitial cells of cajal in sprouty homolog 4 deficient mice. PLoS ONE. 2015;10:e0124861 pubmed publisher
    ..b>Sprouty homolog 4, a known negative regulator of ERK pathway, has been identified in the interstitial cells of Cajal in the ..
  35. Shen F, Cai W, Feng Z, Chen J, Feng J, Liu Q, et al. Long non-coding RNA SPRY4-IT1 pormotes colorectal cancer metastasis by regulate epithelial-mesenchymal transition. Oncotarget. 2017;8:14479-14486 pubmed publisher
    Colorectal cancer (CRC) remains one of the most common cancers worldwide. Increasing evidence indicates that SPRY4 intronic transcript 1 (SPRY4-IT1) regulate cell growth, differentiation, apoptosis, and cancer progression...
  36. Xu Y, Yao Y, Jiang X, Zhong X, Wang Z, Li C, et al. SP1-induced upregulation of lncRNA SPRY4-IT1 exerts oncogenic properties by scaffolding EZH2/LSD1/DNMT1 and sponging miR-101-3p in cholangiocarcinoma. J Exp Clin Cancer Res. 2018;37:81 pubmed publisher
    ..The expression of SPRY4-IT1 in CCA tissues and cell lines was determined by RT-qPCR, and the association between SPRY4-IT1 transcription ..
  37. Morgani S, Saiz N, Garg V, Raina D, Simon C, Kang M, et al. A Sprouty4 reporter to monitor FGF/ERK signaling activity in ESCs and mice. Dev Biol. 2018;441:104-126 pubmed publisher
    ..readout of FGF/ERK activity by targeting a histone H2B-linked Venus fluorophore to the endogenous locus of Spry4, an early pathway target, and generated Spry4H2B-Venus embryonic stem cells (ESCs) and a derivative ..
  38. Greene M, Kratz C, Mai P, Mueller C, Peters J, Bratslavsky G, et al. Familial testicular germ cell tumors in adults: 2010 summary of genetic risk factors and clinical phenotype. Endocr Relat Cancer. 2010;17:R109-21 pubmed publisher
    ..association studies of predominantly sporadic but also familial cases of TGCT have implicated the KIT-ligand, SPRY4, and BAK1 genes as TGCT risk modifiers...
  39. Jing W, Gao S, Zhu M, Luo P, Jing X, Chai H, et al. Potential diagnostic value of lncRNA SPRY4-IT1 in hepatocellular carcinoma. Oncol Rep. 2016;36:1085-92 pubmed publisher
    ..In the present study, we focused on the expression pattern of lncRNA SPRY4 intronic transcript 1 (SPRY4-IT1) and its clinical significance in HCC diagnostics...
  40. Shi J, Ma X, Su Y, Song Y, Tian Y, Yuan S, et al. MiR-31 Mediates Inflammatory Signaling to Promote Re-Epithelialization during Skin Wound Healing. J Invest Dermatol. 2018;138:2253-2263 pubmed publisher
    ..activates the Ras/mitogen-activated protein kinase signaling by directly targeting Rasa1, Spred1, Spred2, and Spry4, which are negative regulators of the Ras/mitogen-activated protein kinase pathway...
  41. Zhao W, Mazar J, Lee B, Sawada J, Li J, Shelley J, et al. The Long Noncoding RNA SPRIGHTLY Regulates Cell Proliferation in Primary Human Melanocytes. J Invest Dermatol. 2016;136:819-828 pubmed publisher
    The long noncoding RNA SPRIGHTLY (formerly SPRY4-IT1), which lies within the intronic region of the SPRY4 gene, is up-regulated in human melanoma cells compared to melanocytes...
  42. Zhou M, Zhang X, Yu X. Overexpression of the long non-coding RNA SPRY4-IT1 promotes tumor cell proliferation and invasion by activating EZH2 in hepatocellular carcinoma. Biomed Pharmacother. 2017;85:348-354 pubmed publisher
    ..The long non-coding RNA SPRY4 intronic transcript 1 (SPRY4-IT1) has been reported in some cancer including regulating cell growth, ..
  43. Weidle U, Birzele F, Kollmorgen G, Rüger R. Long Non-coding RNAs and their Role in Metastasis. Cancer Genomics Proteomics. 2017;14:143-160 pubmed
    ..Finally, under category III, we discuss lncRNAs BANCR, FRLnc1, SPRY4-IT1 and LIMT with partially or poorly-resolved mode of action and varying degree of validation in clinical ..
  44. Xie M, Nie F, Sun M, Xia R, Liu Y, Zhou P, et al. Decreased long noncoding RNA SPRY4-IT1 contributing to gastric cancer cell metastasis partly via affecting epithelial-mesenchymal transition. J Transl Med. 2015;13:250 pubmed publisher
    ..b>SPRY4-IT1 (SPRY4 intronic transcript 1), a lncRNA derived from an intron within SPRY4 gene, involves in multiple cancers ..
  45. Cui F, Wu D, He X, Wang W, Xi J, Wang M. Long noncoding RNA SPRY4-IT1 promotes esophageal squamous cell carcinoma cell proliferation, invasion, and epithelial-mesenchymal transition. Tumour Biol. 2016;37:10871-6 pubmed publisher
    ..Long noncoding RNAs (lncRNAs) are found to be dysregulated in a variety of cancers, including ESCC. SPRY4-IT1 has been recently revealed as oncogenic regulator or tumor suppressors in different cancers; however, whether ..
  46. Tan W, Song Z, Xu Q, Qu X, Li Z, Wang Y, et al. Up-Regulated Expression of SPRY4-IT1 Predicts Poor Prognosis in Colorectal Cancer. Med Sci Monit. 2017;23:309-314 pubmed
    BACKGROUND Long non-coding RNA SPRY4 intronic transcript 1 (lncRNA SPRY4-IT1) has been reported to be associated with the progression of several cancers, but its expression level in colorectal cancer (CRC) has rarely been reported...
  47. Percival C, Marangoni P, Tapaltsyan V, Klein O, Hallgrimsson B. The Interaction of Genetic Background and Mutational Effects in Regulation of Mouse Craniofacial Shape. G3 (Bethesda). 2017;7:1439-1450 pubmed publisher
    ..in three members of the Sprouty family of growth factor negative regulators (Spry1, Spry2, or Spry4) in order to explore the impact of epistatic interactions on skull morphology...
  48. Li J, Chen Y, Chen Z, He A, Xie H, Zhang Q, et al. SPRY4-IT1: A novel oncogenic long non-coding RNA in human cancers. Tumour Biol. 2017;39:1010428317711406 pubmed publisher
    ..Among numerous long non-coding RNAs, we focus on Sprouty4-Intron 1 (SPRY4-IT1), a well-known long non-coding RNA that is overexpressed in various kinds of tumor tissues and cell lines...
  49. Liu D, Li Y, Luo G, Xiao X, Tao D, Wu X, et al. LncRNA SPRY4-IT1 sponges miR-101-3p to promote proliferation and metastasis of bladder cancer cells through up-regulating EZH2. Cancer Lett. 2017;388:281-291 pubmed publisher
    ..Previous studies have suggested that overexpression of SPRY4-IT1 predicates poor prognosis and promotes tumor progress in several cancers...
  50. Vanas V, Mühlbacher E, Kral R, Sutterlüty Fall H. Sprouty4 interferes with cell proliferation and migration of breast cancer-derived cell lines. Tumour Biol. 2014;35:4447-56 pubmed publisher
    ..Additionally, Sprouty4 expression negatively influences cell migration. These data suggest that Sprouty4 is a possible candidate for a tumor suppressor in breast cancer. ..
  51. Xue Liang J, Ming Dong W, Ya Bi Z, Wang Yue W. Upregulated long noncoding RNA SPRY4-IT1 contributes to increased cell viability by activating zinc finger 703 expression in esophageal squamous cell carcinoma. Indian J Cancer. 2015;52 Suppl 3:E164-7 pubmed publisher
    The function of long noncoding RNA SPRY4-IT1 in human esophageal squamous cell carcinoma (ESCC) has been showed in the former studies...
  52. Zhao X, Zhao Z, Xu W, Hou J, Du X. Increased expression of SPRY4-IT1 predicts poor prognosis and promotes tumor growth and metastasis in bladder cancer. Int J Clin Exp Pathol. 2015;8:1954-60 pubmed
    ..In this study, we focused on lncRNA SPRY4-IT1 and investigated its expression pattern, clinical significance, and biological function in UCB...
  53. Yao Y, Gao P, Chen L, Wang W, Zhang J, Li Q, et al. Upregulated long non-coding RNA SPRY4-IT1 predicts dismal prognosis for pancreatic ductal adenocarcinoma and regulates cell proliferation and apoptosis. Gene. 2018;659:52-58 pubmed publisher
    ..b>SPRY4-intronic transcript 1 (SPRY4-IT1) was reported to be upregulated in some kind of human cancers...
  54. Miao Y, Cui L, Chen Z, Zhang L. Gene expression profiling of DMU-212-induced apoptosis and anti-angiogenesis in vascular endothelial cells. Pharm Biol. 2016;54:660-6 pubmed publisher
    ..RAB23, SPHK1, CHSY3, PLAU, PLA2G4C, and MMP10), and genes involved in signal transduction (TMEM217, DUSP8, and SPRY4), chromosome organization (HIST1H2BH and GEM), cell migration and angiogenesis (ERRFI1, HBEGF, and NEDD9), and ..
  55. Liu H, Lv Z, Guo E. Knockdown of long noncoding RNA SPRY4-IT1 suppresses glioma cell proliferation, metastasis and epithelial-mesenchymal transition. Int J Clin Exp Pathol. 2015;8:9140-6 pubmed
    ..b>SPRY4-IT1, belonging to a group of intron-retained lncRNAs, was reported to affect tumor development of many types of ..
  56. Zhang C, Li R, Qi Y, Li X, Yang Y, Liu D, et al. Upregulation of long noncoding RNA SPRY4-IT1 promotes metastasis of esophageal squamous cell carcinoma via induction of epithelial-mesenchymal transition. Cell Biol Toxicol. 2016;32:391-401 pubmed publisher
    ..In the present study, we find that the expression of lncRNA SPRY4-IT1 is significantly upregulated in ESCC cell lines as compared with human esophageal epithelial cell line HEEC...
  57. Klimaschewski L, Sueiro B, Millan L. siRNA mediated down-regulation of Sprouty2/4 diminishes ischemic brain injury. Neurosci Lett. 2016;612:48-51 pubmed publisher
    ..A single injection of Sprouty2/4 siRNAs (25μM each) significantly decreased Spry2 and Spry4 mRNA levels two days later and diminished the size of the injury area in the subchronic phase following ..
  58. Li N, Tan Q, Jing W, Luo P, Tu J. Long Non-Coding RNA SPRY4-IT1 Can Predict Unfavorable Prognosis and Lymph Node Metastasis: a Meta-Analysis. Pathol Oncol Res. 2017;23:731-736 pubmed publisher
    ..This quantitative meta-analysis collected all relevant articles to investigated the association of SPRY4-IT1 expression status with overall survival (OS) and lymph node metastasis (LNM)...
  59. Wang M, Dong X, Feng Y, Sun H, Shan N, Lu T. Prognostic role of the long non-coding RNA, SPRY4 Intronic Transcript 1, in patients with cancer: a meta-analysis. Oncotarget. 2017;8:33713-33724 pubmed publisher
    ..The present study performed a meta-analysis to investigate whether lncRNA, SPRY4 Intronic Transcript 1(SPRY4-IT1) can be served as a potential biomarker for prognosis in human cancers...
  60. Xu Y, Qiu M, Chen Y, Wang J, Xia W, Mao Q, et al. Long noncoding RNA, tissue differentiation-inducing nonprotein coding RNA is upregulated and promotes development of esophageal squamous cell carcinoma. Dis Esophagus. 2016;29:950-958 pubmed publisher
    ..indicates that some lncRNAs are widely involved in the development and progression of ESCC, such as HOTAIR, SPRY4-IT1 and POU3F3...
  61. Wen X, Han X, Wang Y, Fan S, Zhuang J, Zhang Z, et al. Effects of long noncoding RNA SPRY4-IT1-mediated EZH2 on the invasion and migration of lung adenocarcinoma. J Cell Biochem. 2018;119:1827-1840 pubmed publisher
    We aim to investigate the interaction between the EZH2 and the long noncoding RNA (lncRNA) SPRY4-IT1. We also explore their respective effects on human lung adenocarcinoma (LA) cell invasion and migration...
  62. Chung C, Kanetsky P, Wang Z, Hildebrandt M, Koster R, Skotheim R, et al. Meta-analysis identifies four new loci associated with testicular germ cell tumor. Nat Genet. 2013;45:680-5 pubmed publisher
    ..These new TGCT susceptibility loci contain biologically plausible genes encoding proteins important for male germ cell development, chromosomal segregation and the DNA damage response. ..
  63. Rathmanner N, Haigl B, Vanas V, Doriguzzi A, Gsur A, Sutterlüty Fall H. Sprouty2 but not Sprouty4 is a potent inhibitor of cell proliferation and migration of osteosarcoma cells. FEBS Lett. 2013;587:2597-605 pubmed publisher
    ..Sequences within the NH2-terminus are responsible for the specific inhibitory function of Sprouty2 protein. ..
  64. Masoumi Moghaddam S, Amini A, Wei A, Robertson G, Morris D. Sprouty 2 protein, but not Sprouty 4, is an independent prognostic biomarker for human epithelial ovarian cancer. Int J Cancer. 2015;137:560-70 pubmed publisher
    ..In the present study, the expression status of Spry2 and Spry4 proteins and its clinical relevance in human epithelial ovarian cancer (EOC) were investigated retrospectively...
  65. Guo Q, Zhang H, Zhao X, Fu Y, Zhang J, Li M. Loss of expressions of Dusp6, Sprouty4, and Sef, negative regulators of FGF2/ERK1/2 signaling, in the endometrium of women with adenomyosis. Int J Gynecol Pathol. 2014;33:288-97 pubmed publisher
    ..We conclude that downregulation of Dusp6, Sprouty4, and Sef--negative modulators of FGF2/ERK1/2 signaling--was present in eutopic endometria of adenomyosis, which may play critical roles in the development of adenomyosis. ..
  66. So W, Cheng J, Liu Y, Xu C, Zhao J, Chang V, et al. Sprouty4 mediates amphiregulin-induced down-regulation of E-cadherin and cell invasion in human ovarian cancer cells. Tumour Biol. 2016;37:9197-207 pubmed publisher
    ..The down-regulation of SPRY4 expression has been reported in human ovarian cancer...
  67. Leeksma O, Van Achterberg T, Tsumura Y, Toshima J, Eldering E, Kroes W, et al. Human sprouty 4, a new ras antagonist on 5q31, interacts with the dual specificity kinase TESK1. Eur J Biochem. 2002;269:2546-56 pubmed
    ..The two proteins colocalize in apparent cytoplasmic vesicles and do not show substantial translocation to the plasma membrane upon receptor tyrosine kinase stimulation. ..
  68. Chandramouli S, Yu C, Yusoff P, Lao D, Leong H, Mizuno K, et al. Tesk1 interacts with Spry2 to abrogate its inhibition of ERK phosphorylation downstream of receptor tyrosine kinase signaling. J Biol Chem. 2008;283:1679-91 pubmed
    ..By selectively modulating the downstream effects of Spry2, Tesk1 may thus serve as a molecular determinant of the signaling outcome. ..
  69. Sasaki A, Taketomi T, Wakioka T, Kato R, Yoshimura A. Identification of a dominant negative mutant of Sprouty that potentiates fibroblast growth factor- but not epidermal growth factor-induced ERK activation. J Biol Chem. 2001;276:36804-8 pubmed
    ..Finding a dominant negative form of Sproutys will facilitate the study of the molecular mechanism and physiological function of Sproutys. ..
  70. Mason J, Morrison D, Bassit B, Dimri M, Band H, Licht J, et al. Tyrosine phosphorylation of Sprouty proteins regulates their ability to inhibit growth factor signaling: a dual feedback loop. Mol Biol Cell. 2004;15:2176-88 pubmed
    ..Thus, these data highlight a novel negative and positive regulatory loop that allows for the controlled, homeostatic inhibition of RTK signaling. ..
  71. Sharma B, Joshi S, Sassano A, Majchrzak B, Kaur S, Aggarwal P, et al. Sprouty proteins are negative regulators of interferon (IFN) signaling and IFN-inducible biological responses. J Biol Chem. 2012;287:42352-60 pubmed publisher
    ..In other studies, we found that siRNA-mediated knockdown of Spry1, Spry2, or Spry4 promotes IFN-inducible antileukemic effects in vitro and results in enhanced suppressive effects on malignant ..
  72. Ru N, Liang J, Zhang F, Wu W, Wang F, Liu X, et al. SPRY4 Intronic Transcript 1 Promotes Epithelial-Mesenchymal Transition Through Association with Snail1 in Osteosarcoma. DNA Cell Biol. 2016;35:290-5 pubmed publisher
    ..Due to pulmonary metastasis, the 5-year survival rate is still unsatisfactory. It has been reported that SPRY4 intronic transcript 1 (SPRY4-IT1) promotes cell growth, invasion, and inhibits apoptosis in several cancers...
  73. Doriguzzi A, Haigl B, Gsur A, Sutterlüty Fall H. The increased Sprouty4 expression in response to serum is transcriptionally controlled by Specific protein 1. Int J Biochem Cell Biol. 2015;64:220-8 pubmed publisher
    ..These data demonstrate that Specific protein 1 plays a crucial role in the regulation of Sprouty4 in response to serum. ..
  74. Haigl B, Mayer C, Siegwart G, Sutterlüty H. Sprouty4 levels are increased under hypoxic conditions by enhanced mRNA stability and transcription. Biol Chem. 2010;391:813-21 pubmed publisher
    ..In addition, Spry4, one member of this protein family, has been shown to regulate angiogenesis by inhibiting vascular endothelial ..
  75. Alves Ferreira M, Pinho T, Sousa A, Sequeiros J, Lemos C, Alonso I. Identification of genetic risk factors for maxillary lateral incisor agenesis. J Dent Res. 2014;93:452-8 pubmed publisher
    ..We selected 8 genes-MSX1, PAX9, AXIN2, EDA, SPRY2, TGFA, SPRY4, and WNT10A-and performed one of the largest case-control studies taking into account the number of genes and ..
  76. Marcotte E, Pankratz N, Amatruda J, Frazier A, Krailo M, Davies S, et al. Variants in BAK1, SPRY4, and GAB2 are associated with pediatric germ cell tumors: A report from the children's oncology group. Genes Chromosomes Cancer. 2017;56:548-558 pubmed publisher
    ..We accounted for multiple comparisons using a Bonferroni correction. A variant in SPRY4 (rs4624820) was associated with reduced risk of GCT (OR [95% CI]: 0.70 [0.57, 0.86])...
  77. Miraoui H, Dwyer A, Sykiotis G, Plummer L, CHUNG W, Feng B, et al. Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. Am J Hum Genet. 2013;92:725-43 pubmed publisher
    ..other genes were found to be mutated in CHH individuals: FGF17 (n = 3 individuals), IL17RD (n = 8), DUSP6 (n = 5), SPRY4 (n = 14), and FLRT3 (n = 3)...
  78. Kitai H, Ebi H, Tomida S, Floros K, Kotani H, Adachi Y, et al. Epithelial-to-Mesenchymal Transition Defines Feedback Activation of Receptor Tyrosine Kinase Signaling Induced by MEK Inhibition in KRAS-Mutant Lung Cancer. Cancer Discov. 2016;6:754-69 pubmed publisher
    ..expressed but suppressed by the negative regulator Sprouty proteins; MEK inhibition led to repression of SPRY4 and subsequent FGFR1-mediated reactivation of MEK and AKT...
  79. Fukaya T, Someya K, Hibino S, Okada M, Yamane H, Taniguchi K, et al. Loss of Sprouty4 in T cells ameliorates experimental autoimmune encephalomyelitis in mice by negatively regulating IL-1? receptor expression. Biochem Biophys Res Commun. 2014;447:471-8 pubmed publisher
    ..Thus, Sprouty4 and ERK play a critical role in developing iTh17 cells in Th17 cell-driven autoimmune diseases. ..
  80. Ramsdale R, Jorissen R, Li F, Al Obaidi S, Ward T, Sheppard K, et al. The transcription cofactor c-JUN mediates phenotype switching and BRAF inhibitor resistance in melanoma. Sci Signal. 2015;8:ra82 pubmed publisher
  81. Ng C, Jackson R, Buschdorf J, Sun Q, Guy G, Sivaraman J. Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates. EMBO J. 2008;27:804-16 pubmed publisher
  82. Zhang E, Han L, Yin D, He X, Hong L, Si X, et al. H3K27 acetylation activated-long non-coding RNA CCAT1 affects cell proliferation and migration by regulating SPRY4 and HOXB13 expression in esophageal squamous cell carcinoma. Nucleic Acids Res. 2017;45:3086-3101 pubmed publisher
    ..Complex 2 (PRC2) while 3΄ domain of CCAT1 binding SUV39H1) and modulate the histone methylation of promoter of SPRY4 (sprouty RTK signaling antagonist 4) in nucleus...
  83. Zhou H, Sun Z, Li S, Wang X, Zhou X. LncRNA SPRY4-IT was concerned with the poor prognosis and contributed to the progression of thyroid cancer. Cancer Gene Ther. 2018;25:39-46 pubmed publisher
    Long non-coding RNAs (lncRNAs) have been demonstrated to be critical regulators in tumorigenesis. LncRNA SPRY4-IT1 has been identified as critical regulator for hepatocellular carcinoma and ovarian cancer...
  84. Wang J, Thompson B, Ren C, Ittmann M, Kwabi Addo B. Sprouty4, a suppressor of tumor cell motility, is down regulated by DNA methylation in human prostate cancer. Prostate. 2006;66:613-24 pubmed
    ..Sprouty4 expression is down regulated in human prostate cancer by DNA methylation and this decreased expression may contribute to increased cell migration. ..
  85. Yang X, Gong Y, Tang Y, Li H, He Q, Gower L, et al. Spry1 and Spry4 differentially regulate human aortic smooth muscle cell phenotype via Akt/FoxO/myocardin signaling. PLoS ONE. 2013;8:e58746 pubmed publisher
    ..Here, we report for the first time that Spry1, but not Spry4, is required for maintaining the differentiated state of human VSMC in vitro...
  86. Mazar J, Zhao W, Khalil A, Lee B, Shelley J, Govindarajan S, et al. The functional characterization of long noncoding RNA SPRY4-IT1 in human melanoma cells. Oncotarget. 2014;5:8959-69 pubmed
    Expression of the long noncoding RNA (lncRNA) SPRY4-IT1 is low in normal human melanocytes but high in melanoma cells. siRNA knockdown of SPRY4-IT1 blocks melanoma cell invasion and proliferation, and increases apoptosis...
  87. Chai Z, Fan H, Li Y, Song L, Jin X, Yu J, et al. miR-1908 as a novel prognosis marker of glioma via promoting malignant phenotype and modulating SPRY4/RAF1 axis. Oncol Rep. 2017;38:2717-2726 pubmed publisher
    ..shorter survival time of glioma patients via promoting cell proliferation, invasion, anti-apoptosis and regulating SPRY4/RAF1 axis...
  88. Kousa Y, Roushangar R, Patel N, Walter A, Marangoni P, Krumlauf R, et al. IRF6 and SPRY4 Signaling Interact in Periderm Development. J Dent Res. 2017;96:1306-1313 pubmed publisher
    ..Oral adhesions can result from a disruption of periderm formation. Here, we find that IRF6 and SPRY4 signaling interact in periderm function...
  89. Zaharieva I, Georgieva L, Nikolov I, Kirov G, Owen M, O Donovan M, et al. Association study in the 5q31-32 linkage region for schizophrenia using pooled DNA genotyping. BMC Psychiatry. 2008;8:11 pubmed publisher
    ..The predicted associations were confirmed for two of the markers: D5S2017, localised in the SPRY4-FGF1 locus (p = 0.004) and IL9, localized within the IL9 gene (p = 0.014)...
  90. Yu J, Han Q, Cui Y. Decreased long non-coding RNA SPRY4-IT1 contributes to ovarian cancer cell metastasis partly via affecting epithelial-mesenchymal transition. Tumour Biol. 2017;39:1010428317709129 pubmed publisher
    ..The dysregulation of long non-coding RNAs, such as the SPRY4-IT1 (SPRY4 intronic transcript 1), has been associated with various types of malignancies...
  91. Zhang X, Chi Q, Zhao Z. Up-regulation of long non-coding RNA SPRY4-IT1 promotes tumor cell migration and invasion in lung adenocarcinoma. Oncotarget. 2017;8:51058-51065 pubmed publisher
    ..Here, we identified a four-lncRNA signature (SPRY4-IT1, LINC00941,GPR158-AS1 and KCNK15-AS1) displaying prognostic values for LUAD using The ..
  92. Atay S, Wilkey D, Milhem M, Merchant M, Godwin A. Insights into the Proteome of Gastrointestinal Stromal Tumors-Derived Exosomes Reveals New Potential Diagnostic Biomarkers. Mol Cell Proteomics. 2018;17:495-515 pubmed publisher
    ..that in vitro and in vivo-derived GDE, carry proteins associated with IM response, such as Sprouty homolog 4 (SPRY4), surfeit 4 (SURF4), ALIX, and the cGMP-dependent 3',5'-cyclic phosphodiesterase 2A (PDE2A)...