Splice Variant of Heparanase Skipping Exon 12

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2024 Aug 29

PMID 39202399

Authors

Nicola J Nasser

Eviatar Nevo

Aaron Avivi

Affiliations

Soon will be listed here.

Abstract

The subterranean blind mole rat, , has evolved significantly over 47 million years to thrive in its underground habitat. A key enzyme in this adaptation is heparanase, which degrades heparan sulfate (HS) in the extracellular matrix (ECM), facilitating angiogenesis and releasing growth factors for endothelial cells. heparanase has various splice variants influencing tumor growth and metastasis differently. We report a novel splice variant from a hypoxia-exposed kidney sample resulting from exon 12 skipping. This variant maintains the translation frame but lacks enzymatic activity, offering insights into 's unique adaptations.

References

Dong J, Kukula A, Toyoshima M, Nakajima M . Genomic organization and chromosome localization of the newly identified human heparanase gene. Gene. 2000; 253(2):171-8. DOI: 10.1016/s0378-1119(00)00251-1. View

Nasser N, Avivi A, Vlodavsky I, Nevo E . Cloning of two splice variants of Spalax heparanase encoding for truncated proteins. Anticancer Drugs. 2020; 31(9):885-889. DOI: 10.1097/CAD.0000000000000932. View

Edoute Y, Arieli R, Nevo E . Evidence for improved myocardial oxygen delivery and function during hypoxia in the mole rat. J Comp Physiol B. 1988; 158(5):575-82. DOI: 10.1007/BF00692566. View

Levy-Adam F, Abboud-Jarrous G, Guerrini M, Beccati D, Vlodavsky I, Ilan N . Identification and characterization of heparin/heparan sulfate binding domains of the endoglycosidase heparanase. J Biol Chem. 2005; 280(21):20457-66. DOI: 10.1074/jbc.M414546200. View

Friedmann Y, Vlodavsky I, Aingorn H, Aviv A, Peretz T, PECKER I . Expression of heparanase in normal, dysplastic, and neoplastic human colonic mucosa and stroma. Evidence for its role in colonic tumorigenesis. Am J Pathol. 2000; 157(4):1167-75. PMC: 1850180. DOI: 10.1016/S0002-9440(10)64632-9. View

Nasser N . Heparanase involvement in physiology and disease. Cell Mol Life Sci. 2008; 65(11):1706-15. PMC: 11131613. DOI: 10.1007/s00018-008-7584-6. View

Nasser N, Kaplan M, Nevo E, Aviram M . Lipid profile and serum characteristics of the blind subterranean mole rat, Spalax. PLoS One. 2009; 4(2):e4528. PMC: 2639698. DOI: 10.1371/journal.pone.0004528. View

Nevo E, Heth G, Pratt H . Seismic communication in a blind subterranean mammal: a major somatosensory mechanism in adaptive evolution underground. Proc Natl Acad Sci U S A. 1991; 88(4):1256-60. PMC: 50996. DOI: 10.1073/pnas.88.4.1256. View

Sun H, Ye K, Liu D, Pan D, Gu S, Wang Z . Evolution of Hemoglobin Genes in a Subterranean Rodent Species (). Biology (Basel). 2020; 9(5). PMC: 7284791. DOI: 10.3390/biology9050106. View

10.

Fang X, Nevo E, Han L, Levanon E, Zhao J, Avivi A . Genome-wide adaptive complexes to underground stresses in blind mole rats Spalax. Nat Commun. 2014; 5:3966. DOI: 10.1038/ncomms4966. View

11.

Avivi A, Shams I, Joel A, Lache O, Levy A, Nevo E . Increased blood vessel density provides the mole rat physiological tolerance to its hypoxic subterranean habitat. FASEB J. 2005; 19(10):1314-6. DOI: 10.1096/fj.04-3414fje. View

12.

Nasser N, Nevo E, Shafat I, Ilan N, Vlodavsky I, Avivi A . Adaptive evolution of heparanase in hypoxia-tolerant Spalax: gene cloning and identification of a unique splice variant. Proc Natl Acad Sci U S A. 2005; 102(42):15161-6. PMC: 1257723. DOI: 10.1073/pnas.0507279102. View

13.

Daly S, Urquhart J, Hilton E, Mckenzie E, Kammerer R, Lewis M . Mutations in HPSE2 cause urofacial syndrome. Am J Hum Genet. 2010; 86(6):963-9. PMC: 3032078. DOI: 10.1016/j.ajhg.2010.05.006. View

14.

Zhang Q, Ming J, Li Y, Zhang S, Li B, Qiu X . Heparanase expression correlates with angiogenesis and lymphangiogenesis in human lung cancer. Zhongguo Fei Ai Za Zhi. 2010; 12(8):864-7. DOI: 10.3779/j.issn.1009-3419.2009.08.06. View

15.

Vornicova O, Naroditsky I, Boyango I, Shachar S, Mashiach T, Ilan N . Prognostic significance of heparanase expression in primary and metastatic breast carcinoma. Oncotarget. 2018; 9(5):6238-6244. PMC: 5814208. DOI: 10.18632/oncotarget.23560. View

16.

Vlodavsky I, Friedmann Y, Elkin M, Aingorn H, Atzmon R, Bitan M . Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis. Nat Med. 1999; 5(7):793-802. DOI: 10.1038/10518. View

17.

Fux L, Feibish N, Cohen-Kaplan V, Gingis-Velitski S, Feld S, Geffen C . Structure-function approach identifies a COOH-terminal domain that mediates heparanase signaling. Cancer Res. 2009; 69(5):1758-67. PMC: 2650747. DOI: 10.1158/0008-5472.CAN-08-1837. View

18.

Widmer H, Hoppeler H, Nevo E, Taylor C, Weibel E . Working underground: respiratory adaptations in the blind mole rat. Proc Natl Acad Sci U S A. 1997; 94(5):2062-7. PMC: 20043. DOI: 10.1073/pnas.94.5.2062. View

19.

Gross-Cohen M, Yanku Y, Kessler O, Barash U, Boyango I, Cid-Arregui A . Heparanase 2 (Hpa2) attenuates tumor growth by inducing Sox2 expression. Matrix Biol. 2021; 99:58-71. DOI: 10.1016/j.matbio.2021.05.001. View

20.

Nasser N, Avivi A, Shushy M, Vlodavsky I, Nevo E . Cloning, expression, and characterization of an alternatively spliced variant of human heparanase. Biochem Biophys Res Commun. 2007; 354(1):33-8. PMC: 1852469. DOI: 10.1016/j.bbrc.2006.12.189. View