DCTN2 inhibited cellular senescence through targeting TRIM21 mediated MST2 ubiquitination and activation in hepatocellular carcinoma.
8 affiliations
- 1Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, 266000, China.
- 2Yunnan Key Laboratory of Breast Cancer Precision Medicine, Institute of Biomedical Engineering, Kunming Medical University, Kunming, 650500, Yunnan, China.
- 3Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, School of Life Sciences, Yunnan University, Kunming 650500, China.
- 4Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, 637100, China.
- 5School of Pharmacy, Qingdao University, Qingdao 266021, China.
- 6The Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, China.
- 7School of Nursing, Qingdao University, Qingdao 266021, China.
- 8Yunnan Key Laboratory of Breast Cancer Precision Medicine, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Yunnan Hospital of Peking University Cancer Hospital, Kunming, 650118, Yunnan, China.
Abstract
Rationale
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, and inducing cellular senescence presents a promising therapeutic approach. However, the mechanisms underlying senescence in HCC pathogenesis remain unclear. This study investigated key genes involved in liver cancer senescence.Methods
Bioinformatic analyses of HCC datasets identified senescence-related genes, highlighting dynactin subunit 2 (DCTN2). We investigated DCTN2's biological function and regulatory mechanism, analyzed its association with patient prognosis, evaluated the synergistic effects of vilazodone and sorafenib in vitro and in vivo, and examined tumor protein p53 (TP53) mutation-mediated regulation of DCTN2.Results
DCTN2 was identified as a novel HCC senescence-associated gene, whose expression was transcriptionally upregulated by TP53 mutation. DCTN2 knockdown induced cellular senescence, thereby inhibiting HCC cell proliferation, migration, invasion and angiogenesis, whereas its overexpression exerted an opposite oncogenic effect. DCTN2 repressed cellular senescence via interaction with TRIM21, which decreased MST2 K63-linked polyubiquitination and ultimately attenuated the Hippo signaling pathway; DCTN2 overexpression correlated with poor HCC prognosis. Moreover, targeting TRIM21 with vilazodone and sorafenib synergistically induced HCC cellular senescence in vitro and in vivo.Conclusions
Our findings revealed that DCTN2 suppresses cellular senescence by inhibiting the Hippo signaling pathway in HCC. Targeting the DCTN2/TRIM21/MST2 axis, along with TP53 mutation regulation, offers new therapeutic insights for HCC treatment.
Related
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BibTeX
@article{wang2026dctn2,
title = {{DCTN2 inhibited cellular senescence through targeting TRIM21 mediated MST2 ubiquitination and activation in hepatocellular carcinoma.}},
author = {Yanbo Wang and Yaomei He and Qin Yu and Ningrui Wang and Qiaoling Ruan and Haiyan Wang and Hanqing Zhao and Yonglin Zhang and Yang Ke and Caie Tang and Liqi Lang and Yuxia Tang and Lixia Liu and Hao Zhang and Shan Yan and Aimin Wang and Qiushuo Shen and Ceshi Chen},
journal = {Theranostics},
year = {2026},
month = sep,
doi = {10.7150/thno.137790},
url = {https://europepmc.org/article/MED/42909918},
note = {CC BY},
}
RIS
TY - JOUR
TI - DCTN2 inhibited cellular senescence through targeting TRIM21 mediated MST2 ubiquitination and activation in hepatocellular carcinoma.
AU - Yanbo Wang
AU - Yaomei He
AU - Qin Yu
AU - Ningrui Wang
AU - Qiaoling Ruan
AU - Haiyan Wang
AU - Hanqing Zhao
AU - Yonglin Zhang
AU - Yang Ke
AU - Caie Tang
AU - Liqi Lang
AU - Yuxia Tang
AU - Lixia Liu
AU - Hao Zhang
AU - Shan Yan
AU - Aimin Wang
AU - Qiushuo Shen
AU - Ceshi Chen
PY - 2026
DA - 2026/09/03
JO - Theranostics
DO - 10.7150/thno.137790
UR - https://europepmc.org/article/MED/42909918
AB - Rationale Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, and inducing cellular senescence presents a promising therapeutic approach. However, the mechanisms underlying senescence in HCC pathogenesis remain unclear. This study investigated key genes involved in liver cancer senescence.Methods Bioinformatic analyses of HCC datasets identified senescence-related genes, highlighting dynactin subunit 2 (DCTN2). We investigated DCTN2's biological function and regulatory mechanism, analyzed its association with patient prognosis, evaluated the synergistic effects of vilazodone and sorafenib in vitro and in vivo, and examined tumor protein p53 (TP53) mutation-mediated regulation of DCTN2.Results DCTN2 was identified as a novel HCC senescence-associated gene, whose expression was transcriptionally upregulated by TP53 mutation. DCTN2 knockdown induced cellular senescence, thereby inhibiting HCC cell proliferation, migration, invasion and angiogenesis, whereas its overexpression exerted an opposite oncogenic effect. DCTN2 repressed cellular senescence via interaction with TRIM21, which decreased MST2 K63-linked polyubiquitination and ultimately attenuated the Hippo signaling pathway; DCTN2 overexpression correlated with poor HCC prognosis. Moreover, targeting TRIM21 with vilazodone and sorafenib synergistically induced HCC cellular senescence in vitro and in vivo.Conclusions Our findings revealed that DCTN2 suppresses cellular senescence by inhibiting the Hippo signaling pathway in HCC. Targeting the DCTN2/TRIM21/MST2 axis, along with TP53 mutation regulation, offers new therapeutic insights for HCC treatment.
SN - 1838-7640
ER -