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Updated: Jul 9, 2025
Techniques to Induce and Quantify Cellular Senescence
Published on: May 1, 2017
TRAF2 inhibits senescence in hepatocellular carcinoma cells via regulating the ROMO1/ NAD+/SIRT3/SOD2 axis
Jiping Yao1, Xue Liang2, Siduo Xu3
1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310003, China; Department of Gastroenterology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, China.
Abstract:
The suppression of tumor proliferation via cellular senescence has emerged as a promising approach for anti-tumor therapy. Tumor necrosis factor receptor-associated factor 2 (TRAF2), an adaptor protein involved in the NF-κB signaling pathway and reactive oxygen species (ROS) production, has been implicated in hepatocellular carcinoma (HCC) proliferation. However, little is currently known about whether TRAF2 promotes HCC development by inhibiting cellular senescence. Replicative senescence model and IR-induced mouse model demonstrated that TRAF2 expression was decrease in senescence cells or liver tissues. Depletion of TRAF2 could inhibit proliferation and arrest the cell cycle via activating p53/p21WAF1 and p16INK4a/pRb signaling pathways in HCC cells and eventually lead to cellular senescence. Mechanistically, TRAF2 deficiency increased the expression of mitochondrial protein reactive oxygen species modulator 1 (ROMO1) and subsequently activated the NAD+/SIRT3/SOD2 pathway to promote the production of ROS and cause mitochondrial dysfunction, which eventually contributed to DNA damage response (DDR). Our findings demonstrate that TRAF2 deficiency inhibits the proliferation of HCC by promoting senescence. Therefore, targeting TRAF2 through various approaches holds therapeutic potential for treating HCC.
Insights
Targeting Tumor Necrosis Factor Receptor-Associated Factor 2 (TRAF2) inhibits hepatocellular carcinoma (HCC) proliferation by inducing cellular senescence. TRAF2 depletion activates key cell cycle arrest pathways and promotes ROS production, offering a new therapeutic strategy for HCC.
Area of Science:
- Oncology
- Cellular Biology
- Molecular Medicine
Background:
- Cellular senescence is a key mechanism for tumor suppression.
- Tumor Necrosis Factor Receptor-Associated Factor 2 (TRAF2) is implicated in hepatocellular carcinoma (HCC) proliferation.
- The role of TRAF2 in regulating HCC cellular senescence remains unclear.
Purpose of the Study:
- To investigate the role of TRAF2 in the regulation of hepatocellular carcinoma (HCC) cellular senescence.
- To explore the potential of targeting TRAF2 as an anti-cancer therapeutic strategy.
Main Methods:
- Utilized replicative senescence and IR-induced mouse models.
- Assessed TRAF2 expression in senescence and HCC tissues.
- Investigated the effects of TRAF2 depletion on HCC cell proliferation and cell cycle.
- Analyzed the involvement of p53/p21WAF1 and p16INK4a/pRb signaling pathways.
- Examined the impact of TRAF2 deficiency on mitochondrial function, ROS production, and DNA damage response (DDR).
Main Results:
- TRAF2 expression decreased in senescent cells and liver tissues.
- TRAF2 depletion inhibited HCC cell proliferation and induced cell cycle arrest via p53/p21WAF1 and p16INK4a/pRb pathways, leading to senescence.
- TRAF2 deficiency enhanced ROS production and mitochondrial dysfunction through the NAD+/SIRT3/SOD2 pathway, triggering DDR.
- These findings indicate TRAF2 deficiency promotes HCC cellular senescence.
Conclusions:
- TRAF2 deficiency inhibits hepatocellular carcinoma (HCC) proliferation by promoting cellular senescence.
- Targeting TRAF2 presents a promising therapeutic avenue for HCC treatment.
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