PTEN: An Emerging Potential Target for Therapeutic Intervention in Respiratory Diseases

Overview

Journal Oxid Med Cell Longev

Publisher Wiley

Specialties Cell Biology
Endocrinology

Date 2022 Jul 11

PMID 35814272

Authors

Bangrong Cai

Liu Yang

Young Do Jung

Ying Zhang

Xinguang Liu

Peng Zhao

Jiansheng Li

Affiliations

Soon will be listed here.

Abstract

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a potent tumor suppressor that regulates several key cellular processes, including proliferation, survival, genomic integrity, migration, and invasion, via PI3K-dependent and independent mechanisms. A subtle decrease in PTEN levels or catalytic activity is implicated not only in cancer but also in a wide spectrum of other diseases, including various respiratory diseases. A systemic overview of the advances in the molecular and cellular mechanisms of PTEN involved in the initiation and progression of respiratory diseases may offer novel targets for the development of effective therapeutics for the treatment of respiratory diseases. In the present review, we highlight the novel findings emerging from current research on the role of PTEN expression and regulation in airway pathological conditions such as asthma/allergic airway inflammation, pulmonary hypertension (PAH), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and other acute lung injuries (ALI). Moreover, we discuss the clinical implications of PTEN alteration and recently suggested therapeutic possibilities for restoration of PTEN expression and function in respiratory diseases.

Citing Articles

The Relationship Between Differential Expression of Non-coding RNAs (TP53TG1, LINC00342, MALAT1, DNM3OS, miR-126-3p, miR-200a-3p, miR-18a-5p) and Protein-Coding Genes (PTEN, FOXO3) and Risk of Idiopathic Pulmonary Fibrosis.

Korytina G, Markelov V, Gibadullin I, Zulkarneev S, Nasibullin T, Zulkarneev R Biochem Genet. 2025; .

PMID: 39881079 DOI: 10.1007/s10528-024-11012-z.

A miRNA-21-Mediated PTEN/Akt/NF-κB Axis Promotes Chronic Obstructive Pulmonary Disease Pathogenesis.

Sai X, Qin C, Zhang Z, Yu H, Bian T Int J Chron Obstruct Pulmon Dis. 2024; 19:1141-1151.

PMID: 38817823 PMC: 11137736. DOI: 10.2147/COPD.S453593.

Mechanism of KLF9 in airway inflammation in chronic obstructive pulmonary.

Gu P, Wang Z, Yu X, Wu N, Wu L, Li Y Immun Inflamm Dis. 2023; 11(10):e1043.

PMID: 37904708 PMC: 10568256. DOI: 10.1002/iid3.1043.

Small Extracellular Vesicles and Their Involvement in Cancer Resistance: An Up-to-Date Review.

Slomka A, Kornek M, Cho W Cells. 2022; 11(18).

PMID: 36139487 PMC: 9496799. DOI: 10.3390/cells11182913.

References

Tamura M, Gu J, Matsumoto K, Aota S, Parsons R, Yamada K . Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science. 1998; 280(5369):1614-7. DOI: 10.1126/science.280.5369.1614. View

Zhu Y, Wu Y, Shi W, Wang J, Yan X, Wang Q . Inhibition of ubiquitin proteasome function prevents monocrotaline-induced pulmonary arterial remodeling. Life Sci. 2017; 173:36-42. DOI: 10.1016/j.lfs.2017.02.007. View

Li J, Wei L, Han Z, Chen Z . Mesenchymal stromal cells-derived exosomes alleviate ischemia/reperfusion injury in mouse lung by transporting anti-apoptotic miR-21-5p. Eur J Pharmacol. 2019; 852:68-76. DOI: 10.1016/j.ejphar.2019.01.022. View

Yang J, Mao M, Zhen Y . miRNA-23a has effects to improve lung injury induced by sepsis in vitro and vivo study. Biomed Pharmacother. 2018; 107:81-89. DOI: 10.1016/j.biopha.2018.07.097. View

Huang S, White E, Wettlaufer S, Grifka H, Hogaboam C, Thannickal V . Prostaglandin E(2) induces fibroblast apoptosis by modulating multiple survival pathways. FASEB J. 2009; 23(12):4317-26. PMC: 2812040. DOI: 10.1096/fj.08-128801. View

Zhang H, Ding Y, Hou Y, Liu Y, Zhou Z, Nie H . Bone marrow mesenchymal stem cells derived miRNA-130b enhances epithelial sodium channel by targeting PTEN. Respir Res. 2020; 21(1):329. PMC: 7731743. DOI: 10.1186/s12931-020-01595-7. View

Kimura M, Hashimoto N, Kusunose M, Aoyama D, Sakamoto K, Miyazaki S . Exogenous induction of unphosphorylated PTEN reduces TGFβ-induced extracellular matrix expressions in lung fibroblasts. Wound Repair Regen. 2016; 25(1):86-97. DOI: 10.1111/wrr.12506. View

Wang X, Liu M, Zhu M, Shi L, Liu L, Zhao Y . Resveratrol protects the integrity of alveolar epithelial barrier via SIRT1/PTEN/p-Akt pathway in methamphetamine-induced chronic lung injury. Cell Prolif. 2020; 53(3):e12773. PMC: 7106965. DOI: 10.1111/cpr.12773. View

Choi W, Choe S, Lin J, Borchers M, Kosmider B, Vassallo R . Exendin-4 restores airway mucus homeostasis through the GLP1R-PKA-PPARγ-FOXA2-phosphatase signaling. Mucosal Immunol. 2020; 13(4):637-651. PMC: 7664156. DOI: 10.1038/s41385-020-0262-1. View

10.

Zhang H, You L, Zhao M . Rosiglitazone attenuates paraquat-induced lung fibrosis in rats in a PPAR gamma-dependent manner. Eur J Pharmacol. 2019; 851:133-143. DOI: 10.1016/j.ejphar.2019.02.037. View

11.

Gu T, Zhang Z, Wang J, Guo J, Shen W, Yin Y . CREB is a novel nuclear target of PTEN phosphatase. Cancer Res. 2011; 71(8):2821-5. PMC: 3105967. DOI: 10.1158/0008-5472.CAN-10-3399. View

12.

Chen H, Guo S, Zhang S, Li X, Wang H, Li X . MiRNA-620 promotes TGF-β1-induced proliferation of airway smooth muscle cell through controlling PTEN/AKT signaling pathway. Kaohsiung J Med Sci. 2020; 36(11):869-877. DOI: 10.1002/kjm2.12260. View

13.

Baker J, Vuppusetty C, Colley T, Papaioannou A, Fenwick P, Donnelly L . Oxidative stress dependent microRNA-34a activation via PI3Kα reduces the expression of sirtuin-1 and sirtuin-6 in epithelial cells. Sci Rep. 2016; 6:35871. PMC: 5073335. DOI: 10.1038/srep35871. View

14.

Miyoshi K, Yanagi S, Kawahara K, Nishio M, Tsubouchi H, Imazu Y . Epithelial Pten controls acute lung injury and fibrosis by regulating alveolar epithelial cell integrity. Am J Respir Crit Care Med. 2012; 187(3):262-75. DOI: 10.1164/rccm.201205-0851OC. View

15.

Lan H, Zhong H, Gao Y, Ren D, Chen L, Zhang D . The PTEN tumor suppressor inhibits human airway smooth muscle cell migration. Int J Mol Med. 2010; 26(6):893-9. DOI: 10.3892/ijmm_00000539. View

16.

Liu Y, Yang K, Shi H, Xu J, Zhang D, Wu Y . MiR-21 modulates human airway smooth muscle cell proliferation and migration in asthma through regulation of PTEN expression. Exp Lung Res. 2015; 41(10):535-45. DOI: 10.3109/01902148.2015.1090501. View

17.

Barnes P . Cellular and molecular mechanisms of chronic obstructive pulmonary disease. Clin Chest Med. 2014; 35(1):71-86. DOI: 10.1016/j.ccm.2013.10.004. View

18.

Li D, Sun H . TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta. Cancer Res. 1997; 57(11):2124-9. View

19.

Xia J, Yang L, Dong L, Niu M, Zhang S, Yang Z . Cefminox, a Dual Agonist of Prostacyclin Receptor and Peroxisome Proliferator-Activated Receptor-Gamma Identified by Virtual Screening, Has Therapeutic Efficacy against Hypoxia-Induced Pulmonary Hypertension in Rats. Front Pharmacol. 2018; 9:134. PMC: 5829529. DOI: 10.3389/fphar.2018.00134. View

20.

Liu H, Yin T, Yan W, Si R, Wang B, Chen M . Dysregulation of microRNA-214 and PTEN contributes to the pathogenesis of hypoxic pulmonary hypertension. Int J Chron Obstruct Pulmon Dis. 2017; 12:1781-1791. PMC: 5485897. DOI: 10.2147/COPD.S104627. View