Comprehensive Analysis Identifies Ameloblastin-Related Competitive Endogenous RNA as a Prognostic Biomarker for Testicular Germ Cell Tumour

Abstract

Testicular Germ Cell Tumour (TGCT) is one of the most common tumours in young men. Increasing evidence shows that the extracellular matrix has a key role in the prognosis and metastasis of various human cancers. This study analysed the relationship between the matrix protein ameloblastin (AMBN) and potential biological markers associated with TGCT diagnosis and prognosis. The relationship between AMBN and TGCT prognosis was determined by bioinformatic analysis using the expression profiles of three RNAs (long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs) from The Cancer Genome Atlas (TCGA) database, and available clinical information of the corresponding patients. Prediction and validation of competitive endogenous RNA (ceRNA) regulatory networks related to AMBN was performed. AMBN and its associated ceRNA regulatory network were found to be related to the recurrence of TGCT, and LINC02701 may be used as a diagnostic factor in TGCT. Furthermore, we identified PELATON (Plaque Enriched LncRNA In Atherosclerotic And Inflammatory Bowel Macrophage Regulation) as an independent prognostic factor for TGCT progression-free interval.

Revisiting ameloblastin; addressing the EMT-ECM axis above and beyond oral biology

“…Another AMBN promoter analysis (Smith et al, 2020) identified SP6, later suggested to be among the genes implicated in gastric cancer (Zhou et al, 2021) together with MEF2, which resulted from our own AMBN promoter analysis. Our own recent data have associated AMBN expression levels with testicular (Geng et al, 2022) and ovarian cancer (Geng et al, 2023). Thus, the ECM-EMT AMBN association and the GI tract localization data shed a different light on the old promoter data, and the role of these regulatory elements shall be unveiled in future studies.…”

Proteolytic profiles of two isoforms of human AMBN expressed in E. coli by MMP-20 and KLK-4 proteases

“…Ameloblastin (AMBN) represents the most abundant enamel matrix protein from the non-amelogenin protein family [ 9 , 11 , 12 ]. AMBN also possesses additional functions such as the formation of long and cranial bones or its association with the progression of testicular germ cell tumour [ 13 ]. Defects in enamel formation lead to severe diseases, typically to the amelogenesis imperfecta, which is a group of genetically heterogenous hereditary disorders (characteristic for mutations in AMEL, AMBN, ENAM, MMP-20; O60882, KLK-4; Q9Y5K2, etc.)…”

“…The C -terminal part is massively negatively charged with 31 negatively charged residues [ 9 , 28 ], which has a relevancy to the calcium binding [ 9 , 10 , 29 ]. In addition, the calcium binding sites presented in AMBN along with heparin-binding domains and CD63 interaction domains can affect cell adhesion [ 13 ].

Fig.

…”

Hypermethylation of tumor suppressor lncRNA MEF2C-AS1 frequently happened in patients at all stages of colorectal carcinogenesis

“…The elevated expression of BLACAT1 was detected in lesion tissues and was associated with poor prognosis of patients with cervical squamous cell carcinoma (CSCC) [ 15 ] and CRC [ 14 ]. Until now, plenty of functional lncRNAs have been characterized and they might regulate target mRNAs expression through the competitive endogenous RNA (ceRNA) mechanism mediated by miRNAs [ 16 ]. Nevertheless, the potential molecules participating in the specific regulatory network need to be further explored.…”