AKAP12, mediated by transcription factor 21, inhibits cell proliferation, metastasis, and glycolysis in lung squamous cell carcinoma.

A-kinase anchor protein 12 (AKAP12) has been reported to be related to lung squamous cell carcinoma (LUSC) progression. However, its role and molecular mechanisms in LUSC have not been revealed. The mRNA and protein levels of AKAP12 and transcription factor 21 (TCF21) were tested by quantitative real-time PCR and western blot. Cell counting kit 8 assay, EdU assay, flow cytometry, wound healing assay, and transwell assay were used to evaluate cell proliferation, apoptosis, migration, and invasion. Cell glycolysis was measured by testing glucose consumption and lactate production. The interaction between AKAP12 and TCF21 was assessed by ChIP assay and dual-luciferase reporter assay. A mice xenograft model was constructed to explore AKAP12 and TCF21 roles in vivo. Our data showed that AKAP12 was underexpressed in LUSC tissues and cells, and its overexpression inhibited LUSC cell growth, metastasis, and glycolysis. TCF21 had decreased expression in LUSC, which facilitated AKAP12 expression through binding to its promoter region to enhance its transcription. Furthermore, TCF21 increased AKAP12 expression to repress LUSC cell growth, metastasis, and glycolysis. In vivo experiments showed that AKAP12 upregulation reduced LUSC tumorigenesis, and TCF21 knockdown reversed this effect. In conclusion, AKAP12 might be a tumor suppressor in LUSC, which was mediated by TCF21 and could inhibit cell growth, metastasis, and glycolysis to restrain LUSC malignant progression.