MOLECULAR NEUROBIOLOGY
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2025
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IF 4.3
Xu Wenting,Zhou Mengjia,Li Linlin,Zhang Yuqing,Zhang Tianya,Zhang Xiangjian
Activated and polarized microglia regulate neuroinflammatory responses and programmed cell death processes in ischemic stroke. Although the inactivation of muscleblind-like 1 (Mbnl1) is known to cause structural defects in the brain, its role in microglial apoptosis and polarization remains unclear. This study aims to explore the mechanism of Mbnl1 in ischemic stroke, particularly its role in the regulation of microglial apoptosis and polarization, as well as its impact on neuroinflammatory responses and cognitive dysfunction. The expression level of Mbnl1 in the serum of stroke patients was determined. Furthermore, Mbnl1 was overexpressed in a C57BL/6N stroke model and an oxygen-glucose deprivation model in BV-2 cells. Changes in relevant marker proteins were detected using histological assays, cognitive function tests, enzyme-linked immunosorbent assay for inflammatory factor detection, flow cytometry for apoptosis assessment, immunofluorescence, and Western blot analysis. The expression level of Mbnl1 in the serum of stroke patients was determined. Furthermore, Mbnl1 was overexpressed in a C57BL/6N stroke model and an oxygen-glucose deprivation model in BV-2 cells. Changes in relevant marker proteins were detected using histological assays, cognitive function tests, enzyme-linked immunosorbent assay for inflammatory factor detection, flow cytometry for apoptosis assessment, immunofluorescence, and Western blot analysis. Mbnl1 overexpression exerts a protective effect against ischemic stroke by regulating microglia-mediated neuroinflammation through inhibition of the NF-κB signaling pathway. This modulation promotes cognitive recovery in C57BL/6N mice with stroke, highlighting Mbnl1 as a potential therapeutic target for stroke treatment.
研究领域:
神经生物学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ONCOLOGY REPORTS
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2025
·Vol. 54
·期 1
·1-16
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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
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分子生物学
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免疫学
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DOI
PubMed
高影响因子
Journal of Translational Medicine
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2022
·Vol. 20
·期 1
·1-10
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IF 8.44
Huang Kun,Wang Dan-Dan,Hu Wen-Bao,Zeng Wei-Qian,Xu Xia,Li Qiu-Xiang,Bi Fang-Fang,Yang Huan,Qiu Jian
Background Myotonic dystrophy type 1 (DM1), one of the most common forms of adult-onset muscular dystrophy, is caused by abnormally expanded CTG repeats in the 3′ untranslated region of the DMPK gene. The CUG repeats transcribed from the expanded CTG repeats sequestrate a splicing factor, MBNL1, causing the clinical symptoms in DM1. Nowadays, only symptomatic treatments are available for DM1, and no rational therapy is available. Recently, upregulation of MBNL1 expression has been found to be one of the promising therapies for DM1.Methods All experiments were conducted in the C2C12 myoblasts and HSALR mice, a DM1 mouse model. Real-time PCR and western blot were used to detect the mRNA and protein level, respectively. The rotarod exercise, grip strength and hanging time were used to evaluate the muscle strength of mice.Results In this study, we demonstrated that calcitriol, an active form of vitamin D3, increased MBNL1 in C2C12 mouse myoblasts as well as in HSALR mice model for DM1. In HSALR mice model, calcitriol improved muscle strength, and corrected aberrant splicing in skeletal muscle. Besides, calcitriol reduced the number of central nuclei, and improved muscle histopathology in HSALR mice. In addition, we identified that calcitriol upregulated MBNL1 expression via activating the promoter of Mbnl1 in C2C12 myogenic cells.Conclusion Our study suggests that calcitriol is a potential pharmacological strategy for DM1 that enhances MBNL1 expression.
研究领域:
分子生物学
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神经病学
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药理学
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肌肉骨骼疾病
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICAL RESEARCH
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2026
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IF 4.8
Li Chenhao,Wang Xin,Shi Dongliang,Yang Meng,Yang Wenhua,Chen Liang
Background Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Tumor cells often promote the recruitment and infiltration of tumor-associated macrophages (TAMs). We focused on the effect of ETS-like transcription factor 4 (ELK4) on macrophage infiltration in promoting TNBC progression. Methods The publicly available TNBC dataset (GSE38959) was analyzed and found that ELK4 is significantly upregulated in TNBC tissues. Furthermore, Transwell, CCK-8, clonal formation, and EdU assay examined the regulation of ELK4 on cell invasiveness and proliferation. TNBC patient M2 infiltration was detected by flow cytometry. Dual-luciferase assay and ChIP-qPCR experiments were used to assess the bond between ELK4 and Muscleblind Like Splicing Regulator 1 (MBNL1). Results Analysis of the GSE38959 database indicated that ELK4 expression was upregulated in TNBC. Survival analysis revealed that higher ELK4 expression was associated with poorer prognosis in TNBC patients. Clinically, immunohistochemical staining of ELK4 in 60 TNBC patients’ samples suggested that higher ELK4 expression was associated with advanced TNM stage. Double-immunofluorescence staining for ELK4 and CD68 in TNBC tissues revealed a positive correlation between ELK4 expression and the number of CD68 + M2 macrophages. In vitro experiments, ELK4 overexpression enhanced the proliferation, colony formation, and the migration and invasion ability of TNBC cells. ELK4 knockdown showed opposite effects. Macrophage migration and M2 polarization were promoted when cultured in the conditioned medium derived from ELK4-overexpressing TNBC cells and inhibited in the conditioned medium derived from ELK4-silenced TNBC cells. Furthermore, ELK4 promoted Notch signaling activation in TNBC cells. Notably, ELK4 bound to the MBNL1 promoter and downregulated its activity, which was confirmed via dual-luciferase reporter assay and ChIP-qPCR. Conclusion Taken together, our results demonstrate that ELK4 may affect the Notch1 signaling pathway and promote macrophage M2 infiltration through transcriptional inhibition of MBNL1, ultimately promoting TNBC development.
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高影响因子
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