POU2F1 facilitates the malignant phenotypes and aerobic glycolysis of pituitary adenoma by activating LDHA transcription.

BACKGROUND

Pituitary adenoma (PA) can be benign, invasive, and metastatic, and its invasiveness and metastasis are poor prognosis factors for PA patients. Lactate dehydrogenase A (LDHA) plays a key role in glycolysis, and its overexpression can promote PA cell proliferation and invasion; however, the underlying mechanisms remain poorly understood.

METHODS

Reverse-transcription quantitative polymerase chain reaction and western blot were used to quantify the expression of target genes. MTT, EdU, and flow cytometry assays were utilized to detect the viability, proliferation, and apoptotic rates of HP75 cells, respectively. The invasion and migration of HP75 cells were measured by invasion and wound healing assays, and the sphere formation ability of HP75 cells was analyzed by sphere formation assay. The aerobic glycolysis of HP75 cells was tested by the corresponding kits. The JASPAR, GeneCards, and PROMO databases were used to predict the potential transcription factors of LDHA. The interaction between POU domain class 2 transcription factor 1 (POU2F1) and LDHA was verified by dual-luciferase reporter and chromatin immunoprecipitation assays. A xenograft tumor model was constructed to measure the effects of the POU2F1/LDHA axis on tumor growth in vivo.

RESULTS

LDHA was upregulated in PA tissues, and its expression levels in invasive PA tissues were higher than those in non-invasive ones. LDHA knockdown inhibited the proliferation, invasion, migration, sphere formation and aerobic glycolysis of HP75 cells and induced cell apoptosis. Mechanistically, POU2F1 activated LDHA expression to promote the proliferation, invasion, migration, sphere formation and aerobic glycolysis of HP75 cells and to inhibit cell apoptosis. Besides, LDHA overexpression could ameliorate the PI3K/AKT pathway inactivation induced by POU2F1 silence in vivo and in vitro. LDHA overexpression also alleviated the POU2F1 knockdown-induced inhibitory effect on tumor growth in vivo.

CONCLUSION

POU2F1-LDHA axis is up-regulated in pituitary adenomas and represents a potential therapeutic target for this disease.