CDKN3 in cancer: context-dependent cell-cycle control and implications for genome stability and therapy
- 1Department of Oncology, Affiliated Hospital of North Sichuan Medical College
- 2Key Laboratory of Integrated Precision Diagnosis and Treatment for Solid Tumors, Sichuan Provincial Health Commission
- 3Department of Pain, People’s Hospital of Yilong County
Abstract
Cyclin-dependent kinase inhibitor 3 (CDKN3), also known as kinase-associated phosphatase (KAP), dephosphorylates activating cyclin-dependent kinase 2 (CDK2) Thr160, yet high expression is associated with aggressive features in some cancers. This review distinguishes messenger RNA (mRNA) expression, protein abundance, phosphatase activity, functional dependency, prognostic association, and treatment-response prediction. Renal studies include selected perturbation evidence, whereas lung studies cited here primarily report prognostic or computational associations. Hepatocellular carcinoma (HCC) findings remain directionally discordant across analytes, etiologies, models, and endpoints. Recent triple-negative breast cancer (TNBC) studies include transcriptomic and cell-perturbation evidence, as well as a separate cell and murine mammary fat-pad graft study, while an ultraviolet (UV)-induced skin-cancer study identifies a sex- and context-specific protective axis. These results do not support a universal CDKN3 role. A CDKN3-specific connection to chromosomal instability (CIN) and cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) signaling remains unvalidated. Micronuclei and CIN do not invariably activate cGAS–STING. Bulk immune signatures and survival associations alone cannot establish direct immune regulation, functional dependency, or treatment sensitivity. This focused narrative review compares molecular measurements, genetic perturbations, clinical associations, and selected computational studies. We outline matched assays, genetic rescue, longitudinal CIN measurements, and pathway-specific tests needed to determine whether CDKN3 is a context-specific dependency, a biomarker, or a therapeutic target.
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BibTeX
@article{li2026cdkn3,
title = {{CDKN3 in cancer: context-dependent cell-cycle control and implications for genome stability and therapy}},
author = {Yi Li and Long Cheng and Xiaowei Zhang and Zhenkun Zhang and Guobo Du},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1991125},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1991125/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - CDKN3 in cancer: context-dependent cell-cycle control and implications for genome stability and therapy
AU - Yi Li
AU - Long Cheng
AU - Xiaowei Zhang
AU - Zhenkun Zhang
AU - Guobo Du
PY - 2026
DA - 2026/10/30
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1991125
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1991125/full
AB - Cyclin-dependent kinase inhibitor 3 (CDKN3), also known as kinase-associated phosphatase (KAP), dephosphorylates activating cyclin-dependent kinase 2 (CDK2) Thr160, yet high expression is associated with aggressive features in some cancers. This review distinguishes messenger RNA (mRNA) expression, protein abundance, phosphatase activity, functional dependency, prognostic association, and treatment-response prediction. Renal studies include selected perturbation evidence, whereas lung studies cited here primarily report prognostic or computational associations. Hepatocellular carcinoma (HCC) findings remain directionally discordant across analytes, etiologies, models, and endpoints. Recent triple-negative breast cancer (TNBC) studies include transcriptomic and cell-perturbation evidence, as well as a separate cell and murine mammary fat-pad graft study, while an ultraviolet (UV)-induced skin-cancer study identifies a sex- and context-specific protective axis. These results do not support a universal CDKN3 role. A CDKN3-specific connection to chromosomal instability (CIN) and cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) signaling remains unvalidated. Micronuclei and CIN do not invariably activate cGAS–STING. Bulk immune signatures and survival associations alone cannot establish direct immune regulation, functional dependency, or treatment sensitivity. This focused narrative review compares molecular measurements, genetic perturbations, clinical associations, and selected computational studies. We outline matched assays, genetic rescue, longitudinal CIN measurements, and pathway-specific tests needed to determine whether CDKN3 is a context-specific dependency, a biomarker, or a therapeutic target.
SN - 2234-943X
ER -