ANOS1 Facilitated Tumorigenesis in Gastric Cancer through the Regulation of Oxidative Phosphorylation Pathway

TL;DR

This study finds that ANOS1 promotes gastric cancer by altering tumor cell metabolism and influencing the immune environment.

Contribution

The novel contribution is identifying ANOS1 as a key regulator of gastric cancer through oxidative phosphorylation and its impact on immune infiltration.

Findings

ANOS1 is highly expressed in gastric cancer and promotes tumor cell migration, invasion, and proliferation.

ANOS1 knockdown increases oxidative phosphorylation and reduces glycolysis in tumor cells.

ANOS1 expression correlates with M2-type macrophage abundance in the tumor microenvironment.

Abstract

Gastric cancer (GC) is the fifth leading cause of cancer-related deaths, with poor early detection and prognosis. Biomarkers related to its development are desperately needed. This study explores ANOS1 expression in GC and its mechanism in tumor metabolic reprogramming. Core molecules were identified via co-expression analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data. RT-PCR and Western blot were used to confirm the levels of ANOS1 in GC and normal tissues. Assays conducted both in vitro and in vivo verified that ANOS1 accelerates the development of GC. Seahorse XF was used to quantify oxygen consumption rate and extracellular acidification rate as well as glucose absorption, lactate generation, and mtROS levels. Finally, the correlation between the ANOS1 and immune infiltration in gastric cancer was analyzed. Weighted Gene Co-expression Network Analysis of TCGA and GEO datasets identified 44 candidates, from which six prognostic genes were further pinpointed using univariate Cox and least absolute shrinkage and selection operator regression analyses. Gene Set Enrichment Analysis revealed ANOS1 as a potential core regulator. ANOS1 was highly expressed in GC and promoted migration, invasion, and proliferation. Mechanistically, knockdown of ANOS1 promotes oxidative phosphorylation via the receptor tyrosine kinase pathway, suppresses glycolysis, and inhibits the proliferative, migratory, and invasive capacities of tumor cells. The results of immune infiltration analysis revealed that ANOS1 expression was exhibited a positive correlation with the abundance of M2-type macrophages. ANOS1 is up-regulated in GC. As a key regulatory factor of gastric cancer, ANOS1 is involved in the metabolic regulation of tumor cells and may have an impact on prognosis and the immune microenvironment.

Figures