Among the ~22,000 human genes, very few remain that have unknown functions. One such example is suprabasin (SBSN). Originally described as a component of the cornified envelope, the function of stratified epithelia-expressed SBSN is unknown. Both the lack of knowledge about the gene role under physiological conditions and the emerging link of SBSN to various human diseases, including cancer, attract research interest. The association of SBSN expression with poor prognosis of patients suffering from oesophageal carcinoma, glioblastoma multiforme, and myelodysplastic syndromes suggests that SBSN may play a role in human tumourigenesis. Three SBSN isoforms code for the secreted proteins with putative function as signalling molecules, yet with poorly described effects. In this first review about SBSN, we summarised the current knowledge accumulated since its original description, and we discuss the potential mechanisms and roles of SBSN in both physiology and pathology.

• Klíčová slova
• MAPK signalling, cancer resistance, cancer stem-like cells, immunity, interferon, suprabasin,
• MeSH
• diferenciační antigeny * genetika   metabolismus   MeSH
• karcinogeneze * genetika   metabolismus   MeSH
• lidé MeSH
• nádorové proteiny * genetika   metabolismus   MeSH
• nádory * genetika   metabolismus   MeSH
• regulace genové exprese u nádorů * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• diferenciační antigeny * MeSH
• nádorové proteiny * MeSH
• SBSN protein, human MeSH Prohlížeč

Myelodysplastic syndromes (MDS) are preleukemic disorders characterized by clonal growth of mutant hematopoietic stem and progenitor cells. MDS are associated with proinflammatory signaling, dysregulated immune response, and cell death in the bone marrow (BM). Aging, autoinflammation and autoimmunity are crucial features of disease progression, concordant with promoting growth of malignant clones and accumulation of mutations. Suprabasin (SBSN), a recently proposed proto-oncogene of unknown function, physiologically expressed in stratified epithelia, is associated with poor prognosis of several human malignancies. Here, we showed that SBSN is expressed in the BM by myeloid cell subpopulations, including myeloid-derived suppressor cells, and is secreted into BM plasma and peripheral blood of MDS patients. The highest expression of SBSN was present in a patient group with poor prognosis. SBSN levels in the BM correlated positively with blast percentage and negatively with CCL2 chemokine levels and lymphocyte count. In vitro treatment of leukemic cells with interferon-gamma and demethylating agent 5-azacytidine (5-AC) induced SBSN expression. This indicated that aberrant cytokine levels in the BM and epigenetic landscape modifications in MDS patients may underlie ectopic expression of SBSN. Our findings suggest SBSN as a candidate biomarker of high-risk MDS with a possible role in disease progression and therapy resistance.

• Klíčová slova
• 5-azacytidine, MDS, MDSCs, biomarker, suprabasin,
• MeSH
• azacytidin farmakologie   MeSH
• biologické markery krev   metabolismus   MeSH
• chemokin CCL2 metabolismus   MeSH
• diferenciační antigeny krev   genetika   metabolismus   MeSH
• HEK293 buňky MeSH
• interferon gama farmakologie   MeSH
• kompartmentace buňky účinky léků   MeSH
• kostní dřeň metabolismus   MeSH
• leukocyty mononukleární metabolismus   MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• myelodysplastické syndromy krev   metabolismus   MeSH
• myeloidní buňky účinky léků   metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádorové proteiny krev   genetika   metabolismus   MeSH
• počet lymfocytů MeSH
• prognóza MeSH
• protoonkogen Mas MeSH
• regulace genové exprese u nádorů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• azacytidin MeSH
• biologické markery MeSH
• chemokin CCL2 MeSH
• diferenciační antigeny MeSH
• interferon gama MeSH
• MAS1 protein, human MeSH Prohlížeč
• messenger RNA MeSH
• nádorové proteiny MeSH
• protoonkogen Mas MeSH
• SBSN protein, human MeSH Prohlížeč