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

Kong,Gyeyeong; Lee,Hyunji; Vo,Thuy-Trang T.; Juang,Uijin; Kwon,So Hee; Park,Jisoo; Park,Jongsun; Kim,Seon-Hwan

doi:10.3892/mmr.2022.12814

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

Authors:
- Gyeyeong Kong
- Hyunji Lee
- Thuy-Trang T. Vo
- Uijin Juang
- So Hee Kwon
- Jisoo Park
- Jongsun Park
- Seon-Hwan Kim
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Affiliations: Department of Pharmacology, Metabolic Syndrome and Cell Signaling Laboratory, Institute for Cancer Research, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea, College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, Republic of Korea, Mitos Research Institute, Mitos Therapeutics Inc., Daejeon 34134, Republic of Korea, Department of Neurosurgery, Institute for Cancer Research, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea
Published online on: August 4, 2022 https://doi.org/10.3892/mmr.2022.12814
Article Number: 298
Copyright: © Kong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

cAMP and cGMP are important secondary messengers involved in cell regulation and metabolism driven by the G protein‑coupled 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 AC‑stimulatory 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 N‑terminal 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 mini‑review summarizes the location of PDE11A expression, the impact of structural differences and disease relevance.

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