AC129507.1 is a ferroptosis-related target identified by a novel mitochondria-related lncRNA signature that is involved in the tumor immune microenvironment in gastric cancer.

BACKGROUND

Gastric cancer (GC) is one of the most common malignancies. Previous studies have shown that mitochondrial metabolism is associated with malignancies. However, relevant research on mitochondria-related lncRNAs in GC is lacking.

METHODS

We integrated the corresponding information of patients with GC from The Cancer Genome Atlas (TCGA) database. Mitochondria-related lncRNAs were selected based on differential expression and a correlation analysis to construct a prognostic model. The mutation data were analyzed to distinguish differences in the tumor mutation burden (TMB). Single-sample gene set enrichment analysis (ssGSEA) was performed to evaluate immunological differences. A series of cell-based experiments were adopted to evaluate the biological behavior of GC.

RESULTS

A total of 1571 mitochondria-related lncRNAs were identified. A prognostic signature incorporating nine lncRNAs was built based on 293 suitable GC cases and could predict patient prognosis. The TMB and ssGSEA indicated that the low-risk group displayed increased immune function. The enrichment analysis indicated that the differentially expressed genes were enriched in metabolic functions. AC129507.1 was significantly upregulated in GC cells and associated with a poor prognosis, and its knockdown inhibited the proliferation and migration of GC cells. Mechanistically, silencing AC129507.1 led to abnormal glycolipid metabolism and oxidative stress, thus inducing ferroptosis.

CONCLUSIONS

Our nine-lncRNA risk signature could powerfully predict patient prognosis. AC129507.1 promoted the malignant phenotypes of GC cells. AC129507.1 could play a nonnegligible role in GC by promoting the formation of a immunosuppressive tumor microenvironment by inhibiting the initiation of ferroptosis, which needs to be further explored.