Dataset Information

Modulation of ST6Gal1 in Prostate Cancer Cells

ABSTRACT: Proteomics analyses using LC-MS/MS was performed on wild-type and ST6Gal1 overexpressing DU145 prostate cancer cells. Total cell lysate and secreted proteins from both were analyzed.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Sharon Pitteri

LAB HEAD: Sharon Pitteri

PROVIDER: PXD041316 | Pride | 2023-11-06

REPOSITORIES: Pride

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			Action	DRS
	EV_Media_shotgunproteomics_031519_01.raw	Raw
	EV_Media_shotgunproteomics_031519_01.raw_20190913_Byonic_database.xlsx	Xlsx
	EV_Media_shotgunproteomics_031519_02.raw	Raw
	EV_Media_shotgunproteomics_031519_02.raw_20190913_Byonic_database.xlsx	Xlsx
	EV_Media_shotgunproteomics_031519_03.raw	Raw

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Publications

ST6GAL1-mediated aberrant sialylation promotes prostate cancer progression.

Scott Emma E Archer Goode Emily E Garnham Rebecca R Hodgson Kirsty K Orozco-Moreno Margarita M Turner Helen H Livermore Karen K Putri Nangkana Kyla K Frame Fiona M FM Bermudez Abel A Jose Garcia Marques Fernando F McClurg Urszula L UL Wilson Laura L Thomas Huw H Buskin Adriana A Hepburn Anastasia A Duxfield Adam A Bastian Kayla K Pye Hayley H Arredondo Hector M HM Hysenaj Gerald G Heavey Susan S Stopka-Farooqui Urszula U Haider Aiman A Freeman Alex A Singh Saurabh S Johnston Edward W EW Punwani Shonit S Knight Bridget B McCullagh Paul P McGrath John J Crundwell Malcolm M Harries Lorna L Heer Rakesh R Maitland Norman J NJ Whitaker Hayley H Pitteri Sharon S Troyer Dean A DA Wang Ning N Elliott David J DJ Drake Richard R RR Munkley Jennifer J

The Journal of pathology 20230807 1

Aberrant glycosylation is a universal feature of cancer cells, and cancer-associated glycans have been detected in virtually every cancer type. A common change in tumour cell glycosylation is an increase in α2,6 sialylation of N-glycans, a modification driven by the sialyltransferase ST6GAL1. ST6GAL1 is overexpressed in numerous cancer types, and sialylated glycans are fundamental for tumour growth, metastasis, immune evasion, and drug resistance, but the role of ST6GAL1 in prostate cancer is po ...[more]

PMID: 37550801

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Project description:Purpose: Available tools for prostate cancer (PC) diagnosis and prognosis are suboptimal and novel biomarkers are urgently needed. Here, we investigated the regulation and biomarker potential of the GABRE~miR-452~miR-224 genomic locus. Experimental design: GABRE/miR-452/miR-224 transcriptional expression was quantified in 80 non-malignant and 281 PC tissue samples. GABRE promoter methylation was determined by methylation-specific qPCR (MethyLight) in 35 non-malignant, 293 PC (radical prostatectomy (RP) cohort 1) and 198 PC tissue samples (RP cohort 2). Diagnostic/prognostic biomarker potential of GABRE methylation was evaluated by ROC, Kaplan-Meier, uni- and multivariate Cox regression analyses. Functional roles of miR-224 and miR-452 were investigated in PC3 and DU145 cells by viability, migration, and invasion assays and gene-set enrichment analysis (GSEA) of post-transfection transcriptional profiling data. Results: GABRE~miR-452~miR-224 was significantly downregulated in PC compared to non-malignant prostate tissue and had highly cancer-specific aberrant promoter hypermethylation (AUC=0.98). Functional studies and GSEA suggested that miR-224 and miR-452 inhibit proliferation, migration, and invasion of PC3 and DU145 cells by direct/indirect regulation of pathways related to the cell cycle and cellular motility. Finally, in uni- and multivariate analyses, high GABRE promoter methylation was significantly associated with biochemical recurrence in RP cohort 1, which was successfully validated in RP cohort 2. Conclusion: The GABRE~miR-452~miR-224 locus is downregulated and hypermethylated in PC and is a new promising epigenetic candidate biomarker for PC diagnosis and prognosis. Tumor suppressive functions of the intronic miR-224 and miR-452 were demonstrated in two PC cell lines, suggesting that epigenetic silencing of GABRE~miR-452~miR-224 may be selected for in PC. Affymetrix GeneChip Human Gene 1.0 ST Arrays were used for whole-genome transcriptional profiling of DU145 and PC3 cells at 48 hours post-transfection with either miR-224, miR-452, or scrambled miRNA mimics, or untransfected. All experiments were performed in duplicate. Transcript expression levels were determined after RMA16 normalization in GeneSpringGX 11.0 software (Agilent). PC3 and DU145 arrays were normalized separately. DU145 48 t Scr2a were excluded from the study because of bad performance of this microarray.