RUNX3-Regulated GALNT6 Promotes the Migration and Invasion of Hepatocellular Carcinoma Cells by Mediating O-Glycosylation of MUC1

Overview

Journal Dis Markers

Publisher Wiley

Specialty Biochemistry

Date 2022 Aug 1

PMID 35909886

Authors

Fei Gao

Gang Zheng

Affiliations

Soon will be listed here.

Abstract

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Dysregulation of messenger RNAs (mRNA) has been recognized to be associated with HCC carcinogenesis and development. Polypeptide GalNAc Transferase 6 (GALNT6), an O-type glycosyltransferase, has been confirmed as tumor promoter in different cancers. However, the function of GALNT6 in HCC remains to be studied.

Methods: RT-qPCR and western blot experiments were, respectively, performed for evaluating RNA expressions and protein levels. Supported by bioinformatics analysis, mechanism assays were conducted for validating the potential relation between different genes. Functional assays were implemented to analyze HCC cell migration and invasion after different transfections.

Results: GALNT6 was aberrantly upregulated in HCC cells. Knockdown of GALNT6 could repress HCC cell migration and invasion. RUNX3 was verified to bind to GALNT6 promoter and activate GALNT6 transcription. GALNT6 depletion led to inhibited O-glycosylation and aggravated degradation of MUC1. MUC1 overexpression could rescue the impeded HCC cell migration and invasion induced by GALNT6 knockdown.

Conclusion: To sum up, GALNT6 transcriptionally activated by RUNX3 mediated the O-glycosylation of MUC1, thus exerting promoting influence on HCC cell migration and invasion.

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