iScience
·
2023
·
IF 5.8
Jiapeng Hu,Ruiwei Ding,Shaozhuang Liu,Jia Wang,Jianjun Li,Yunxiao Shang
Asthma is a global chronic airway disease. The expression and role of RNF125, an E3 ubiquitin ligase, in asthma remain uncertain. In this study, we revealed that RNF125 was downregulated in the bronchial epithelium of mice and patients with asthma. Rnf125 hypermethylation was responsible for the low expression of RNF125 in primary airway epithelial cells of mice treated with OVA. Moreover, we demonstrated that RNF125 could attenuate autophagy, oxidative stress, and protect epithelial barrier in vivo and in vitro . Additionally, we identified HMGB1 as a substrate of RNF125, which interacted with the HMG B-box domain of HMGB1 and induced degradation via the ubiquitin proteasome system, reducing autophagy and oxidative stress. Overall, our findings elucidated that hypermethylation of Rnf125 reduced its expression, which promoted autophagy-induced oxidative stress in asthma by increasing HMGB1 stability. These findings offer a theoretical and experimental basis for the pathogenesis of asthma.
研究领域:
免疫学
·
肺科学
·
分子生物学
·
表观遗传学
✓ 已验证
DOI
PubMed
高影响因子
ONCOLOGY REPORTS
·
2025
·Vol. 54
·期 1
·1-16
·
IF 3.9
Yubo Yan,Xianglong Kong,Xiangyuan Jin,Jianlong Bu,Boxiong Ni,Zuqin Rao,Junnan Guo,Shidong Xu
Ring finger protein 125 (RNF125), a ubiquitin E3 ligase, has been reported to act as a tumor suppressor in several cancers, but its precise function in lung adenocarcinoma (LUAD) has not been elucidated. In the present study, through bioinformatics analysis and immunohistochemistry in LUAD and non‑cancerous samples, it was demonstrated that RNF125 was significantly downregulated in lung cancer. Low levels of RNF125 expression were associated with metastatic status, advanced tumor stage and poor overall survival in LUAD. The results of gain‑ and loss‑of‑function experiments demonstrated that RNF125 inhibited proliferation, colony formation, migration and invasion of LUAD cells. In addition, RNF125 increased the sensitivity of LUAD cells to cisplatin. Mechanistically, RNF125 interacted with programmed cell death ligand 1 (PD‑L1) and reduced PD‑L1 expression levels in LUAD cells. Furthermore, IL‑2 secretion by Jurkat T cells was significantly suppressed when co‑cultured with RNF125‑silenced LUAD cells. NK‑92 cell lysis of RNF125‑silenced LUAD cells was also weaker compared with that of control LUAD cells, suggesting that RNF125 knockdown enhanced the immune evasion ability of LUAD cells. Notably, the results of the present study identified that the RNA‑binding protein muscleblind‑like 1 (MBNL1) is the upstream regulator of RNF125 in LUAD. MBNL1 increased the stability of the RNF125 transcript in LUAD cells and knockdown of RNF125 reversed the antitumor effect of MBNL1 on LUAD cells. In conclusion, the present study demonstrated the tumor suppressor role of RNF125 in LUAD and implicated MBNL1 as an upstream regulator of RNF125 in LUAD. These findings contributed to an improved understanding of the molecular features of LUAD progression.
研究领域:
肿瘤学
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Clinical Oncology
·
2026
·
IF 3
Zhang Peng,Chang Yuan,Yang Xiaolu,He Binglu,Ma Li
Background Breast cancer (BC) represents one of the leading causes of cancer-related mortality in women worldwide. Betulinic acid (BA), a naturally derived pentacyclic triterpenoid, exhibits anti-BC activity. Recent evidence implicates RNF125 , a RING-domain E3 ubiquitin ligase, as a tumor suppressor. This study aimed to elucidate whether BA exerts anti-BC effects via RNF125 regulation and explored the underlying mechanisms. Methods RNF125 -overexpressing or knockdown BC cell lines were generated to examine the regulatory effect on cell proliferation, motility, and invasiveness. Furthermore, a subcutaneous xenograft mouse model was established to evaluate the influence of RNF125 on tumor growth in vivo. Results Bioinformatics analyses revealed BA-mediated upregulation of RNF125 in BC cells. Pan-cancer data indicated reduced RNF125 expression in BC specimens, correlating with unfavorable survival outcomes. Consistently, our results showed that BA upregulates RNF125 protein expression in a concentration-dependent manner. In clinically collected BC samples, diminished RNF125 expression was significantly associated with advanced TNM staging. Functional assays demonstrated that RNF125 overexpression suppressed cell proliferation, migration, and invasion. Conversely, RNF125 knockdown reversed these effects and abrogated BA-mediated suppression of malignant phenotypes in BC cells. Mechanistically, RNF125 interacted with MYH9 (Myosin Heavy Chain 9) to facilitate its ubiquitin-mediated proteasomal degradation. In BA-treated BC cells, the protein expression of MYH9 was inhibited. Ectopic MYH9 expression reversed the tumor-suppressive effects of RNF125 overexpression. Finally, a murine xenograft model confirmed that RNF125 overexpression inhibits BC tumor growth. Conclusion These findings suggested that RNF125 mediates the anti-tumor effect of BA, at least in part, through ubiquitin-dependent degradation of MYH9 . Graphical abstract The alternative text for this image may have been generated using AI.
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2026
·
IF 4.7
Yang Di,Liu Jia,Gao Yan,Guan Xin,Tong Rui
Cervical cancer (CC) is a prevalent malignancy in women; however, the efficacy of immunotherapy in this disease is suboptimal, highlighting the need for novel therapeutic targets. We found that low RNF125 expression correlated with poor prognosis in CC patients. In vitro and in vivo, RNF125 inhibited proliferation and induced apoptosis of CC cells. In immunocompetent mice, RNF125 suppressed tumor growth, increased CD8⁺ T cell infiltration, elevated IFN-γ secretion, and reduced PD-1 expression on CD8⁺ T cells. Co-culture experiments confirmed that tumor cells overexpressing RNF125 enhanced CD8⁺ T cell proliferation and function. Further mechanistic investigation revealed that RNF125 promoted CD8⁺ T cell activity by ubiquitinating and degrading PD-L1. Additionally, RNF125 was identified as a direct target of miR-574-5p. This study demonstrates that RNF125 exhibits tumor-suppressive functions in CC by enhancing anti-tumor immunity, highlighting its therapeutic potential.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Runxiao Lv,Lili Du,Lunhao Bai
Osteoarthritis (OA) is a chronic joint disease characterized by the progressive degradation of articular cartilage. In this study, as determined by histological staining, the cartilage surface of the OA rats was damaged, defective and broken, and chondrocytes and proteoglycan were reduced. While moderate physical exercise showed protective effects on the cartilage. Besides, RNA-seq was performed to select a target protein and RNF125 (an E3 ubiquitin ligase) was decreased in the cartilage tissues of OA rats and increased after physiological exercise. However, the precise role of RNF125 in OA is still unknown. This work aimed to investigate the involvement and underlying mechanism of RNF125 in OA pathogenesis. Our results defined that adenovirus-mediated overexpression of RNF125 inhibited the degradation of extracellular matrix of chondrocytes induced by IL-1β, as revealed by increased chondrocyte viability, upregulated COL2A1 and ACAN levels, and downregulated MMP1, MMP13 and ADAMTS5 levels, which was abrogated by NR4A2 knockdown. In vivo, RNF125 relieved OA, manifested as reduced cartilage injury and increased chondrocytes. Mechanically, NFATC2 bound to the RNF125 promoter and directly regulated RNF125 transcription, as illustrated by luciferase reporter, Ch-IP and DNA pull-down assays. Furthermore, RNF125 overexpression inhibited the nuclear translocation of β-catenin, thus suppressing activation of the Wnt/β-catenin signaling pathway. Also, RNF125 as E3 ubiquitin ligase led to the ubiquitination and degradation of TRIM14 protein, and TRIM14 overexpression efficiently reversed the effects of RNF125 overexpression on OA progression. Totally, this study provides new insights into OA pathogenesis regulated by RNF125. RNF125 may be a novel biomarker for OA therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）