Functional characteristics and research trends of PDE11A in human diseases (Review).

cAMP and cGMP are important secondary messengers involved in cell regulation and metabolism driven by the G protein­coupled receptor. cAMP is converted via adenylyl cyclase (AC) and activates protein kinase A to phosphorylate intracellular proteins that mediate specific responses. cAMP signaling serves a role at multiple steps in tumorigenesis. The level of cAMP is increased in association with cancer cell formation through activation of AC­stimulatory G protein by mutation. Phosphodiesterases (PDEs) hydrolyze cAMP and cGMP to AMP and GMP. PDEs are composed of 11 families, and each can hydrolyze cAMP and cGMP or both cAMP and cGMP. PDEs perform various roles depending on their location and expression site, and are involved in several diseases, including male erectile dysfunction, pulmonary hypertension, Alzheimer's disease and schizophrenia. PDE11A is the 11th member of the PDE family and is characterized by four splice variants with varying tissue expression and N­terminal regulatory regions. Among tissues, the expression of PDE11A was highest in the prostate, and it was also expressed in hepatic skeletal muscle, pituitary, pancreas and kidney. PDE11A is the first PDE associated with an adrenocortical tumor associated genetic condition. In several studies, three PDE11A mutations have been reported in patients with Cushing syndrome with primary pigmented nodular adrenocortical disease or isolated micronodular adrenocortical disease without other genetic defects. It has been reported that an increase in PDE11A expression affects the proliferation of glioblastoma and worsens patient prognosis. The present mini­review summarizes the location of PDE11A expression, the impact of structural differences and disease relevance.

Phosphodiesterase 11 A (PDE11A), a potential biomarker for glioblastoma.

Phosphodiesterase 11A (PDE11A), a 3',5'-cyclic nucleotide phosphodiesterase, is a key regulator of intracellular signaling that functions by degrading cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). However, the function of PDE11A in brain tumors is currently unclear. In this study, we found that PDE11A may be involved in glioblastoma development. The protein and mRNA levels of PDE11A were significantly higher in U87-MG, U251-MG and U343-MG glioblastoma cell lines. Gene expression analyses by deep-sequencing revealed that PDE11A mRNA levels were higher in U87-MG and U251-MG cells compared to other cells in the cerebral cortex. A comprehensive analysis of The Cancer Genome Atlas (TCGA) data revealed that PDE11A expression was also elevated in glioblastoma patients. Taken together, these data indicate that PDE11A expression was increased in glioblastoma cell lines and glioma patients, suggesting that PDE11A could be a putative diagnostic marker and therapeutic target for glioma.