Comprehensive in silico analysis of glycosylphosphatidylinositol- anchored protein (GPI-AP) related genes expression profiles in human normal and cancer tissues
Received date: 2023-03-03
Revised date: 2023-05-20
Online published: 2023-05-31
Supported by
National Natural Science Foundation of China(32071278);National Natural Science Foundation of China(31900923);National Natural Science Foundation of China(31770853)
In human cells, there are more than 146 glycosylphosphatidylinositol-anchored proteins (GPI-APs), including receptors, ligands, adhesion molecules and enzymes. The proteins are associated with membrane microdomains called lipid rafts through GPI, and plays a variety of important biological functions. At present, plenty of studies have been carried out on the biosynthesis of GPI-APs. The biosynthesis of GPI-APs requires at least 20 steps, and more than 40 GPI biosynthetic genes have been identified. However, it remains unclear how expression of GPI-AP related genes is regulated in normal and cancer tissues. In this study, we utilized gene expression data from both the TCGA database and GTEx portal to analysis the gene expression involved in GPI-AP biosynthesis and encoding GPI-APs in normal and cancer tissues. In order to perform a comprehensive analysis, we employed the GlycoMaple, a tool that is specifically designed to analyze glycosylation pathways. The results showed that compared with normal tissues, the expression of genes involved in GPI-AP biosynthesis in cancer tissues such as early glioma, glioblastoma multiforme, pancreatic cancer, testicular germ cell carcinoma, skin primary cutaneous melanoma and skin metastatic cutaneous melanoma, was changed significantly. Particularly, the expression of PIGY in these six cancers was increased. In addition, the expression of CD14, a GPI-AP gene, was increased in these six cancers. The expression of GAS1, GPC2 and GPC4 was increased only in early glioma and glioblastoma multiforme indicating that some GPI-APs such as GAS1 can be used as biomarkers of glioma. This study provides new insights into the expression of GPI-AP related genes in normal and cancer tissues, and lays a solid foundation for the development of GPI-APs as biomarkers.
Weize Kong, Yishi Liu, Xiaodong Gao, Morihisa Fujita . Comprehensive in silico analysis of glycosylphosphatidylinositol- anchored protein (GPI-AP) related genes expression profiles in human normal and cancer tissues[J]. Hereditas(Beijing), 2023 , 45(8) : 669 -683 . DOI: 10.16288/j.yczz.23-043
| [1] | Xia MQ, Hale G, Lifely MR, Ferguson MA, Campbell D, Packman L, Waldmann H. Structure of the CAMPATH-1 antigen, a glycosylphosphatidylinositol-anchored glycoprotein which is an exceptionally good target for complement lysis. Biochem J, 1993, 293(Pt 3): 633-640. |
| [2] | Legan PK, Rau A, Keen JN, Richardson GP. The mouse tectorins. Modular matrix proteins of the inner ear homologous to components of the sperm-egg adhesion system. J Biol Chem, 1997, 272(13): 8791-8801. |
| [3] | Hazenbos WLW, Clausen BE, Takeda J, Kinoshita T. GPI-anchor deficiency in myeloid cells causes impaired FcgammaR effector functions. Blood, 2004, 104(9): 2825-2831. |
| [4] | Kawagoe K, Kitamura D, Okabe M, Taniuchi I, Ikawa M, Watanabe T, Kinoshita T, Takeda J. Glycosylphosphatidylinositol-anchor-deficient mice: implications for clonal dominance of mutant cells in paroxysmal nocturnal hemoglobinuria. Blood, 1996, 87(9): 3600-3606. |
| [5] | Pittet M, Conzelmann A. Biosynthesis and function of GPI proteins in the yeast Saccharomyces cerevisiae. Biochim Biophys Acta, 2007, 1771(3): 405-420. |
| [6] | Ueda Y, Yamaguchi R, Ikawa M, Okabe M, Morii E, Maeda Y, Kinoshita T. PGAP1 knock-out mice show otocephaly and male infertility. J Biol Chem, 2007, 282(42): 30373-30380. |
| [7] | Capurro M, Martin T, Shi W, Filmus J. Glypican-3 binds to Frizzled and plays a direct role in the stimulation of canonical Wnt signaling. J Cell Sci, 2014, 127(Pt 7): 1565-1575. |
| [8] | Capurro MI, Xiang YY, Lobe C, Filmus J. Glypican-3 promotes the growth of hepatocellular carcinoma by stimulating canonical Wnt signaling. Cancer Res, 2005, 65(14): 6245-6254. |
| [9] | Wang DC, Gao Y, Zhang Y, Wang LF, Chen G. Glypican-3 promotes cell proliferation and tumorigenesis through up-regulation of β-catenin expression in lung squamous cell carcinoma. Biosci Rep, 2019, 39(6): BSR20181147. |
| [10] | Nakatsura T, Yoshitake Y, Senju S, Monji M, Komori H, Motomura Y, Hosaka S, Beppu T, Ishiko T, Kamohara H, Ashihara H, Katagiri T, Furukawa Y, Fujiyama S, Ogawa M, Nakamura Y, Nishimura Y. Glypican-3, overexpressed specifically in human hepatocellular carcinoma, is a novel tumor marker. Biochem Biophys Res Commun, 2003, 306(1): 16-25. |
| [11] | Umezu T, Shibata K, Shimaoka M, Kajiyama H, Yamamoto E, Ino K, Nawa A, Senga T, Kikkawa F. Gene silencing of glypican-3 in clear cell carcinoma of the ovary renders it more sensitive to the apoptotic agent paclitaxel in vitro and in vivo. Cancer Sci, 2010, 101(1): 143-148. |
| [12] | Cottereau E, Mortemousque I, Moizard MP, Bürglen L, Lacombe D, Gilbert-Dussardier B, Sigaudy S, Boute O, David A, Faivre L, Amiel J, Robertson R, Viana Ramos F, Bieth E, Odent S, Demeer B, Mathieu M, Gaillard D, Van Maldergem L, Baujat G, Maystadt I, Héron D, Verloes A, Philip N, Cormier-Daire V, Frouté MF, Pinson L, Blanchet P, Sarda P, Willems M, Jacquinet A, Ratbi I, Van Den Ende J, Lackmy-Port Lis M, Goldenberg A, Bonneau D, Rossignol S, Toutain A. Phenotypic spectrum of Simpson-Golabi-Behmel syndrome in a series of 42 cases with a mutation in GPC3 and review of the literature. Am J Med Genet C Semin Med Genet, 2013, 163c(2): 92-105. |
| [13] | Johnson B, Mahadevan D. Emerging role and targeting of carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) in human malignancies. Clin Cancer Drugs, 2015, 2(2): 100-111. |
| [14] | Camacho-Leal P, Zhai AB, Stanners CP. A co-clustering model involving alpha5beta1 integrin for the biological effects of GPI-anchored human carcinoembryonic antigen (CEA). J Cell Physiol, 2007, 211(3): 791-802. |
| [15] | Huang YF, Aoki K, Akase S, Ishihara M, Liu YS, Yang GL, Kizuka Y, Mizumoto S, Tiemeyer M, Gao XD, Aoki- Kinoshita KF, Fujita M. Global mapping of glycosylation pathways in human-derived cells. Dev Cell, 2021, 56(8): 1195-1209.e7. |
| [16] | Goldman MJ, Craft B, Hastie M, Repe?ka K, McDade F, Kamath A, Banerjee A, Luo YH, Rogers D, Brooks AN, Zhu JC, Haussler D. Visualizing and interpreting cancer genomics data via the Xena platform. Nat Biotechnol, 2020, 38(6): 675-678. |
| [17] | UniProt Consortium. UniProt: a hub for protein information. Nucleic Acids Res, 2015, 43(Database issue): D204-D212. |
| [18] | Kinoshita T. Biosynthesis and biology of mammalian GPI-anchored proteins. Open Biol, 2020, 10(3): 190290. |
| [19] | Ashida H, Hong Y, Murakami Y, Shishioh N, Sugimoto N, Kim YU, Maeda Y, Kinoshita T. Mammalian PIG-X and yeast Pbn1p are the essential components of glycosylphosphatidylinositol-mannosyltransferase I. Mol Biol Cell, 2005, 16(3): 1439-1448. |
| [20] | Ohishi K, Inoue N, Kinoshita T.PIG-S and PIG-T, essential for GPI anchor attachment to proteins, form a complex with GAA1 and GPI8. EMBO J, 2001, 20(15): 4088-4098. |
| [21] | Tanaka S, Maeda Y, Tashima Y, Kinoshita T. Inositol deacylation of glycosylphosphatidylinositol-anchored proteins is mediated by mammalian PGAP1 and yeast Bst1p. J Biol Chem, 2004, 279(14): 14256-14263. |
| [22] | Hirata T, Mishra SK, Nakamura S, Saito K, Motooka D, Takada Y, Kanzawa N, Murakami Y, Maeda Y, Fujita M, Yamaguchi Y, Kinoshita T. Identification of a Golgi GPI-N-acetylgalactosamine transferase with tandem transmembrane regions in the catalytic domain. Nat Commun, 2018, 9(1): 405. |
| [23] | Watanabe R, Murakami Y, Marmor MD, Inoue N, Maeda Y, Hino J, Kangawa K, Julius M, Kinoshita T.Initial enzyme for glycosylphosphatidylinositol biosynthesis requires PIG-P and is regulated by DPM2. EMBO J, 2000, 19(16): 4402-4411. |
| [24] | Kajiwara K, Watanabe R, Pichler H, Ihara K, Murakami S, Riezman H, Funato K. Yeast ARV1 is required for efficient delivery of an early GPI intermediate to the first mannosyltransferase during GPI assembly and controls lipid flow from the endoplasmic reticulum. Mol Biol Cell, 2008, 19(5): 2069-2082. |
| [25] | Miyata T, Takeda J, Iida Y, Yamada N, Inoue N, Takahashi M, Maeda K, Kitani T, Kinoshita T. The cloning of PIG-A, a component in the early step of GPI-anchor biosynthesis. Science, 1993, 259(5099): 1318-1320. |
| [26] | Inoue N, Watanabe R, Takeda J, Kinoshita T.PIG-C, one of the three human genes involved in the first step of glycosylphosphatidylinositol biosynthesis is a homologue of Saccharomyces cerevisiae GPI2. Biochem Biophys Res Commun, 1996, 226(1): 193-199. |
| [27] | Kamitani T, Chang HM, Rollins C, Waneck GL, Yeh ET. Correction of the class H defect in glycosylphosphatidylinositol anchor biosynthesis in Ltk- cells by a human cDNA clone. J Biol Chem, 1993, 268(28): 20733-20736. |
| [28] | Watanabe R, Inoue N, Westfall B, Taron CH, Orlean P, Takeda J, Kinoshita T. The first step of glycosylphosphatidylinositol biosynthesis is mediated by a complex of PIG-A, PIG-H, PIG-C and GPI1. EMBO J, 1998, 17(4): 877-885. |
| [29] | Murakami Y, Siripanyaphinyo U, Hong Y, Tashima Y, Maeda Y, Kinoshita T. The initial enzyme for glycosylphosphatidylinositol biosynthesis requires PIG-Y, a seventh component. Mol Biol Cell, 2005, 16(11): 5236-5246. |
| [30] | Fujihara Y, Ikawa M. GPI-AP release in cellular, developmental, and reproductive biology. J Lipid Res, 2016, 57(4): 538-545. |
| [31] | Knaus A, Kortüm F, Kleefstra T, Stray-Pedersen A, ?uki? D, Murakami Y, Gerstner T, van Bokhoven H, Iqbal Z, Horn D, Kinoshita T, Hempel M, Krawitz PM. Mutations in PIGU impair the function of the GPI transamidase complex, causing severe intellectual disability, epilepsy, and brain anomalies. Am J Hum Genet, 2019, 105(2): 395-402. |
| [32] | Paprocka J, Hutny M, Hofman J, Tokarska A, K?aniewska M, Szcza?uba K, Stembalska A, Jezela-Stanek A, ?migiel R. Spectrum of neurological symptoms in glycosylphosphatidylinositol biosynthesis defects: systematic review. Front Neurol, 2022, 12: 758899. |
| [33] | Murakami Y, Tawamie H, Maeda Y, Büttner C, Buchert R, Radwan F, Schaffer S, Sticht H, Aigner M, Reis A, Kinoshita T, Jamra RA. Null mutation in PGAP1 impairing Gpi-anchor maturation in patients with intellectual disability and encephalopathy. PLoS Genet, 2014, 10(5): e1004320. |
| [34] | Granzow M, Paramasivam N, Hinderhofer K, Fischer C, Chotewutmontri S, Kaufmann L, Evers C, Kotzaeridou U, Rohrschneider K, Schlesner M, Sturm M, Pinkert S, Eils R, Bartram CR, Bauer P, Moog U. Loss of function of PGAP1 as a cause of severe encephalopathy identified by whole exome sequencing: lessons of the bioinformatics pipeline. Mol Cell Probes, 2015, 29(5): 323-329. |
| [35] | Davids M, Menezes M, Guo YR, McLean SD, Hakonarson H, Collins F, Worgan L, Billington CJ, Maric I, Littlejohn RO, Onyekweli T, Members Of The U, Adams DR, Tifft CJ, Gahl WA, Wolfe LA, Christodoulou J, Malicdan MCV. Homozygous splice-variants in human ARV1 cause GPI-anchor synthesis deficiency. Mol Genet Metab, 2020, 130(1): 49-57. |
| [36] | Litwack ED, Babey R, Buser R, Gesemann M, O'Leary DDM. Identification and characterization of two novel brain-derived immunoglobulin superfamily members with a unique structural organization. Mol Cell Neurosci, 2004, 25(2): 263-274. |
| [37] | Sharma K, Schmitt S, Bergner CG, Tyanova S, Kannaiyan N, Manrique-Hoyos N, Kongi K, Cantuti L, Hanisch UK, Philips MA, Rossner MJ, Mann M, Simons M. Cell type- and brain region-resolved mouse brain proteome. Nat Neurosci, 2015, 18(12): 1819-1831. |
| [38] | Wang KC, Koprivica V, Kim JA, Sivasankaran R, Guo Y, Neve RL, He ZG. Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth. Nature, 2002, 417(6892): 941-944. |
| [39] | Vourc'h P, Dessay S, Mbarek O, Marouillat Védrine S, Müh JP, Andres C. The oligodendrocyte-myelin glycoprotein gene is highly expressed during the late stages of myelination in the rat central nervous system. Brain Res Dev Brain Res, 2003, 144(2): 159-168. |
| [40] | Lin SR, Yu IS, Huang PH, Tsai CW, Lin SW. Chimaeric mice with disruption of the gene coding for phosphatidylinositol glycan class A (Pig-a) were defective in embryogenesis and spermatogenesis. Br J Haematol, 2000, 110(3): 682-693. |
| [41] | Fujihara Y, Okabe M, Ikawa M. GPI-anchored protein complex, LY6K/TEX101, is required for sperm migration into the oviduct and male fertility in mice. Biol Reprod, 2014, 90(3): 60. |
| [42] | Ciesielska A, Matyjek M, Kwiatkowska K. TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling. Cell Mol Life Sci, 2021, 78(4): 1233-1261. |
| [43] | Pauken KE, Sammons MA, Odorizzi PM, Manne S, Godec J, Khan O, Drake AM, Chen ZY, Sen DR, Kurachi M, Barnitz RA, Bartman C, Bengsch B, Huang AC, Schenkel JM, Vahedi G, Haining WN, Berger SL, Wherry EJ. Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade. Science, 2016, 354(6316): 1160-1165. |
| [44] | Chikaraishi K, Takenobu H, Sugino RP, Mukae K, Akter J, Haruta M, Kurosumi M, Endo TA, Koseki H, Shimojo N, Ohira M, Kamijo T. CFC1 is a cancer stemness-regulating factor in neuroblastoma. Oncotarget, 2017, 8(28): 45046-45059. |
| [45] | Izzi L, Lévesque M, Morin S, Laniel D, Wilkes BC, Mille F, Krauss RS, McMahon AP, Allen BL, Charron F. Boc and Gas1 each form distinct Shh receptor complexes with Ptch1 and are required for Shh-mediated cell proliferation. Dev Cell, 2011, 20(6): 788-801. |
| [46] | Zamorano A, Mellstr?m B, Vergara P, Naranjo JR, Segovia J. Glial-specific retrovirally mediated gas1 gene expression induces glioma cell apoptosis and inhibits tumor growth in vivo. Neurobiol Dis, 2004, 15(3): 483-491. |
| [47] | Shi W, Filmus J. Glypican-6 and Glypican-4 stimulate embryonic stomach growth by regulating Hedgehog and noncanonical Wnt signaling. Dev Dyn, 2022, 251(12): 2015-2028. |
| [48] | Ng W, Pébay A, Drummond K, Burgess A, Kaye AH, Morokoff A. Complexities of lysophospholipid signalling in glioblastoma. J Clin Neurosci, 2014, 21(6): 893-898. |
/
| 〈 |
|
〉 |