Annals of clinical and laboratory science · 2025
Downregulation of PLCXD3 Promotes Gastric Cancer Cell Stemness and Invasiveness as a Potential Early Diagnostic Biomarker.
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Xue Gang, He Lijian
Аннотация
UNLABELLED: Gastric cancer (GC) is a leading cause of cancer-related death worldwide, and insufficient early diagnostic strategies limit patient outcomes. Phospholipase C X-domain containing 3 (PLCXD3) has been implicated in tumor progression, but its role in GC remains unclear. This study aimed to clarify the biological function of PLCXD3 and assess its potential as an early diagnostic biomarker and tumor suppressor in GC.
METHODS: An integrated bioinformatics analysis of three Gene Expression Omnibus (GEO) datasets was performed to identify differentially expressed genes in early gastric cancer tissues. PLCXD3 expression levels were validated in clinical samples and AGS gastric cancer cells. Functional assays, including CCK-8, Transwell, wound-healing, and spheroid formation assays, were conducted to assess the effects of PLCXD3 knockdown and overexpression on cell proliferation, migration, invasion, and stemness. The expression of epithelial-mesenchymal transition (EMT) markers and Wnt/β-catenin pathway-related proteins was examined by qRT-PCR, Western blotting, and immunofluorescence.
RESULTS: PLCXD3 expression was significantly downregulated in early gastric cancer tissues and AGS cells. Silencing PLCXD3 markedly promoted cell proliferation, migration, invasion, EMT progression, and upregulated stemness-associated markers (SOX2, Oct4, NANOG, KLF4). Knockdown of PLCXD3 also activated the Wnt/β-catenin signaling pathway, as evidenced by increased β-catenin, WNT3A, and c-MYC expression. Conversely, PLCXD3 overexpression suppressed these malignant phenotypes.
CONCLUSIONS: PLCXD3 functions as a tumor suppressor in gastric cancer by inhibiting cell migration, invasion, and stemness through modulation of the Wnt/β-catenin pathway. Its downregulation may serve as a novel early diagnostic biomarker and a promising therapeutic target in gastric cancer management.
METHODS: An integrated bioinformatics analysis of three Gene Expression Omnibus (GEO) datasets was performed to identify differentially expressed genes in early gastric cancer tissues. PLCXD3 expression levels were validated in clinical samples and AGS gastric cancer cells. Functional assays, including CCK-8, Transwell, wound-healing, and spheroid formation assays, were conducted to assess the effects of PLCXD3 knockdown and overexpression on cell proliferation, migration, invasion, and stemness. The expression of epithelial-mesenchymal transition (EMT) markers and Wnt/β-catenin pathway-related proteins was examined by qRT-PCR, Western blotting, and immunofluorescence.
RESULTS: PLCXD3 expression was significantly downregulated in early gastric cancer tissues and AGS cells. Silencing PLCXD3 markedly promoted cell proliferation, migration, invasion, EMT progression, and upregulated stemness-associated markers (SOX2, Oct4, NANOG, KLF4). Knockdown of PLCXD3 also activated the Wnt/β-catenin signaling pathway, as evidenced by increased β-catenin, WNT3A, and c-MYC expression. Conversely, PLCXD3 overexpression suppressed these malignant phenotypes.
CONCLUSIONS: PLCXD3 functions as a tumor suppressor in gastric cancer by inhibiting cell migration, invasion, and stemness through modulation of the Wnt/β-catenin pathway. Its downregulation may serve as a novel early diagnostic biomarker and a promising therapeutic target in gastric cancer management.