HKDC1 Silencing Inhibits Proliferation and Glycolysis of Gastric Cancer Cells

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Gastric cancer (GC) is a significant global health challenge, ranking as the third most lethal and fifth most common cancer.
• The hexokinase domain component 1 (HKDC1) has been identified as a potential oncogene implicated in various cancer types.

Purpose of the Study:

• To investigate the specific role of HKDC1 in the development and progression of gastric cancer.
• To elucidate the molecular mechanisms by which HKDC1 influences GC cell behavior and metabolism.

Main Methods:

• Analysis of three Gene Expression Omnibus (GEO) datasets (GSE103236, GSE13861, GSE55696) using sva package and R software.
• Identification of differentially expressed genes (DEGs) and glycolysis-related genes (glyGenes) in the TCGA-STAD cohort via gene set enrichment analysis (GSEA).
• Functional assays including Cell Count Kit-8, oxygen consumption, glucose uptake, lactate production, and ATP level measurements following HKDC1 knockdown in GC cell lines (AGS and MKN-45).

Main Results:

• A total of 411 DEGs were identified in the pooled GC dataset.
• HKDC1 was identified as a prevalent glyGene in GC tumor tissues and cells.
• HKDC1 knockdown significantly reduced GC cell proliferation, suppressed glucose absorption and lactate production, decreased ATP levels, and lowered the extracellular acidification rate, while increasing oxygen consumption.

Conclusions:

• HKDC1 acts as an oncogene in gastric cancer development.
• HKDC1 significantly influences GC cell proliferation and glycolysis.
• Targeting HKDC1 may represent a potential therapeutic strategy for gastric cancer.