N- and O-glycosylation patterns and functional testing of CGB7 versus CGB3/5/8 variants of the human chorionic gonadotropin (hCG) beta subunit

Abstract

The classical function of human chorionic gonadotropin (hCG) is its role in supporting pregnancy. hCG is a dimer consisting of two highly glycosylated subunits, alpha (CGA) and beta (CGB). The beta-hCG protein is encoded by CGB3, CGB5, CGB7 and CGB8 genes. CGB3, 5 and 8 code for an identical protein, CGB3/5/8, whereas CGB7 differs in three amino acids from CGB3/5/8. We had observed earlier that CGB7 and CGB3/5/8 display very distinct tissue expression patterns and that the tumor suppressor and transcription factor p53 can activate expression of CGB7 but not of CGB3/5/8 genes. Here, we investigate the glycan structures and possible functional differences of the two CGB variants. To this end, we established a system to produce and isolate recombinant CGA, CGB7 and CGB3/5/8 proteins. We found that N- and O-glycosylation patterns of CGB7 and CGB3/5/8 are quite similar. Functional assays were performed by testing activation of the ERK1/2 pathway and demonstrated that CGB7 and CGB5/5/8 appear to be functionally redundant isoforms, although a slight difference in the kinetics of ERK1/2 pathway activation was observed. This is the first time that biological activity of CGB7 is shown. In summary, the results lead to the hypothesis that CGB7 and CGB3/5/8 do not hold significant functional differences but that timing and cell type of their expression is the key for understanding their divergent evolution.

Construction of 3D and 2D contrast-enhanced CT radiomics for prediction of CGB3 expression level and clinical prognosis in bladder cancer

“…A previous study has found that in T2-T4 Bca, elevated urinary β-hCG levels before treatment are a brand of poor prognosis [ 9 ]. The beta subunit of hCG is encoded by a set of highly homologous genes (human chorionic gonadotropin beta subunit, CGB, tagged CGB1-CGB9), which also determines its immunological properties [ 10 ]. As an affiliate of the glycoprotein hormone chain family, CGB3 (Chorionic Gonadotropin Subunit Beta 3, CGB, HCGB) encodes the β3 subunit of β-hCG ( https://www.genecards.org/cgi-bin/carddisp.pl?gene=CGB3 ).…”

“…The heterogeneity of cancer is closely related to histobiological features such as the proliferation of the abnormal cell, necrosis, angiogenesis and fibrosis [ 19 ]. Features that were extracted from medical imaging can reflect potential temporal heterogeneity and spatial heterogeneity of tumors, providing effective information for identifying muscle invasion of tumors, pathological grading, and assessing prognosis [ 10 , 20 , 21 ]. Radiomics extracts high-throughput image features and acquires massive image parameters to non-invasively and dynamically detect and quantitatively reflect tumor characteristics.…”