Ubiquitination-Dependent Cyclin Regulation in Gastric Cancer and Emerging Targeted Therapies with Chinese Herbal Bioactive Compounds
- 1School of Life Sciences, , Hangzhou 310053, China; (S.Q.);
- 2Jinhua Academy, , Jinhua 321000, China
- 3Hangzhou Institute of Medicine (HIM), , No. 150 Dongfang Street, Qiantang District, Hangzhou 310053, China
Abstract
Gastric cancer (GC) remains one of the most prevalent malignancies worldwide, with a high mortality rate primarily attributable to late-stage diagnosis and limited therapeutic options. Aberrant cell proliferation arising from cell cycle dysregulation is a hallmark of GC pathogenesis. Cyclins, as core regulators of cell cycle progression, exhibit dynamic protein expression patterns that are tightly controlled by the ubiquitin–proteasome system (UPS). In GC, cyclins are frequently overexpressed due to impaired ubiquitination and subsequent proteasomal degradation. This review systematically elucidates the ubiquitination-mediated regulation of distinct cyclins (Cyclins D, E, A, and B) at specific cell cycle phases—G1, S, G2, and M—and highlights the critical roles of E3 ubiquitin ligases, including SCF complexes and APC/C, in GC progression. We further discuss how dysregulated non-coding RNAs and altered E3 ligase expression contribute to aberrant cyclin ubiquitination, thereby promoting GC cell proliferation, metastasis, and poor prognosis. Importantly, emerging evidence demonstrates that bioactive compounds derived from traditional Chinese medicine (TCM) can counteract these abnormalities by directly downregulating cyclin expression, modulating E3 ligase activity, or inhibiting 26S/20S proteasome function, thus restoring cell cycle homeostasis and suppressing GC growth. This review integrates molecular mechanisms of cyclin ubiquitination with TCM-based therapeutic strategies, offering novel insights into targeted interventions for GC.
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BibTeX
@article{qian2026ubiquitinationdependent,
title = {{Ubiquitination-Dependent Cyclin Regulation in Gastric Cancer and Emerging Targeted Therapies with Chinese Herbal Bioactive Compounds}},
author = {Sicheng Qian and Xinyi Zheng and Jiaqi Li and Jiahan Le and Jiangjiang Qin and Yitao Chen},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18193179},
url = {https://europepmc.org/article/PMC/PMC13664568},
note = {CC BY},
}
RIS
TY - JOUR
TI - Ubiquitination-Dependent Cyclin Regulation in Gastric Cancer and Emerging Targeted Therapies with Chinese Herbal Bioactive Compounds
AU - Sicheng Qian
AU - Xinyi Zheng
AU - Jiaqi Li
AU - Jiahan Le
AU - Jiangjiang Qin
AU - Yitao Chen
PY - 2026
DA - 2026/10/01
JO - Cancers
DO - 10.3390/cancers18193179
UR - https://europepmc.org/article/PMC/PMC13664568
AB - Gastric cancer (GC) remains one of the most prevalent malignancies worldwide, with a high mortality rate primarily attributable to late-stage diagnosis and limited therapeutic options. Aberrant cell proliferation arising from cell cycle dysregulation is a hallmark of GC pathogenesis. Cyclins, as core regulators of cell cycle progression, exhibit dynamic protein expression patterns that are tightly controlled by the ubiquitin–proteasome system (UPS). In GC, cyclins are frequently overexpressed due to impaired ubiquitination and subsequent proteasomal degradation. This review systematically elucidates the ubiquitination-mediated regulation of distinct cyclins (Cyclins D, E, A, and B) at specific cell cycle phases—G1, S, G2, and M—and highlights the critical roles of E3 ubiquitin ligases, including SCF complexes and APC/C, in GC progression. We further discuss how dysregulated non-coding RNAs and altered E3 ligase expression contribute to aberrant cyclin ubiquitination, thereby promoting GC cell proliferation, metastasis, and poor prognosis. Importantly, emerging evidence demonstrates that bioactive compounds derived from traditional Chinese medicine (TCM) can counteract these abnormalities by directly downregulating cyclin expression, modulating E3 ligase activity, or inhibiting 26S/20S proteasome function, thus restoring cell cycle homeostasis and suppressing GC growth. This review integrates molecular mechanisms of cyclin ubiquitination with TCM-based therapeutic strategies, offering novel insights into targeted interventions for GC.
SN - 2072-6694
ER -