Overexpression of Glycosyltransferase 8 Domain Containing 1 Promotes Gastric Cancer Proliferation and Inhibits Apoptosis via Mediating PTPN6/JAK2/STAT3 Signaling Axis.

Abstract

Background: The mechanisms of gastric cancer (GC) occurrence and development are still unclear. Although glycosyltransferase 8 domain containing 1 (GLT8D1) has been implicated in GC, its specific role and molecular mechanisms in GC progression need to be further investigated. Methods: Tissue microarrays were used to detect the expression levels of GLT8D1 in 80 GC tissues and their corresponding non-tumor adjacent tissues. The correlations between the GLT8D1 expression level and clinicopathological characteristics were evaluated. A series of in vitro and in vivo functional experiments were performed to explore the role of GLT8D1 in GC progression. Combined with transcriptomic RNA sequencing (RNA-seq) and Weighted Gene Co-expression Network Analysis (WGCNA), we delineated the potential mechanisms via experimental verification. Results: Elevated expression of GLT8D1 in GC tissues was positively correlated with advanced clinical stages and poor prognosis. Konckdown of GLT8D1 significantly inhibited GC cell proliferation and induced apoptosis, whereas overexpression did the opposite. Further researches demonstrated that protein tyrosine phosphatase non-receptor type 6 (PTPN6), a downstream target of GLT8D1, has the capacity to modulate the activity of the JAK2/STAT3 signaling pathway. Conclusions: Our study indicated that GLT8D1 expression was upregulated in GC tissues and correlated with poor prognosis. We reveal a potential molecular mechanism by which GLT8D1 promotes GC progression.