FEBS LETTERS
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2015
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IF 3.169
Chen Xie,Wei Chen,Mengdie Zhang,Qiuxian Cai,Weiyi Xu,Xiaodi Li,Songshan Jiang
Despite extensive investigation into the role of let-7 miRNAs in pathological tumor processes, their involvement in the DNA damage response remains unclear. Here we show that most let-7 family members down-regulate MDM4 expression via binding to MDM4 mRNA at a conserved DNA sequence. Expression of exogenous let-7 miRNA mimics decreased MDM4 protein but not mRNA levels. Several DNA damage reagents increased let-7 expression, thereby decreasing MDM4 protein levels in glioma cells. Inhibition of endogenous let-7 with antisense RNAs rescued MDM4 protein levels with or without MG132, a proteasome-dependent degradation inhibitor. An MDM4 mutation identified in a glioma patient was associated with loss of the putative MDM4 target site. Therefore, let-7 binding to MDM4 is implicated in the DNA damage response.
研究领域:
癌症生物学
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分子生物学
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遗传学
✓ 已验证
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
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2019
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IF 4.868
Lifang Sun,Min Zhu,Wei Feng,Yiping Lin,Jia Yin,Juan Jin,Yunguang Wang
Idiopathic pulmonary fibrosis (IPF) is a prototype of chronic, progressive, and fibrotic lung disease with high morbidity and high mortality. Menstrual blood-derived stem cells (MenSCs) have proven to be an attractive tool for the treatment of acute lung injury and fibrosis-related diseases through immunosuppression and antifibrosis. However, whether MenSC-derived exosomes have the similar function on pulmonary fibrosis remains unclear. In the present study, exosomes secreted from MenSCs (MenSCs-Exo) were verified by transmission electron microscope (TEM), nanoparticle tracking analyzer (NTA), and western blotting. And MenSC-Exo addition significantly improved BLM-induced lung fibrosis and alveolar epithelial cell damage in mice, mainly reflected in BLM-mediated enhancement of the fibrosis score, blue collagen deposition, dry/wet gravity ratio, hydroxyproline and malondialdehyde levels, and downregulation of glutathione peroxidase, which were all robustly reversed by MenSC-Exo management. Additionally, BLM- and TGF-β1-evoked cellular reactive oxygen species (ROS), mitochondrial DNA (mtDNA) damage, and cell apoptosis were rescued by MenSCs-Exo in vivo and in vitro. Further study indicated that the MenSCs-Exo could transport miRNA Let-7 into recipient alveolar epithelial cells. Let-7 inhibitor administration significantly blocked the exosome-mediated improvement role on lung fibrosis in mice. Mechanistically, Let-7 was able to regulate the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX1) through binding to its 3-UTR region. Forced expression of LOX1 promoted the expression of apoptosis-related protein and mtDNA damage markers via regulating NLRP3 which was also confirmed in BLM model mice under the combination therapy of the exosome and Let-7 inhibitor. Collectively, this study demonstrates that exosomal Let-7 from MenSCs remits pulmonary fibrosis through regulating ROS, mtDNA damage, and NLRP3 inflammasome activation. This provides a new approach of exocytosis on the treatment of fibrotic lung disease.
研究领域:
干细胞生物学
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肺医学
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分子生物学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Neural Regeneration Research
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2020
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IF 3.171
Chao-Qun Lin,Lu-Kui Chen
Previous research found that cerebral dopamine neurotrophic factor (CDNF) has a protective effect on brain dopaminergic neurons, and CDNF is regarded as a promising therapeutic agent for neurodegenerative diseases. However, the effects of CDNF on the proliferation, differentiation, and apoptosis of neural stem cells (NSCs), which are very sensitive to hypoxic environments, remain unknown. In this study, NSCs were extracted from the hippocampi of fetal rats and cultured with different concentrations of CDNF. The results showed that 200 nM CDNF was the optimal concentration for significantly increasing the viability of NSCs under non-hypoxic environmental conditions. Then, the cells were cultured with 200 nM CDNF under the hypoxic conditions of 90% N 2 , 5% CO 2 , and 5% air for 6 hours. The results showed that CDNF significantly improved the viability of hypoxic NSCs and reduced apoptosis among hypoxic NSCs. The detection of markers showed that CDNF increased the differentiation of hypoxic NSCs into neurons and astrocytes. CDNF also reduced the expression level of Lin28 protein and increased the expression of Let-7 mRNA in NSCs, under hypoxic conditions. In conclusion, we determined that CDNF was able to reverse the adverse proliferation, differentiation, and apoptosis effects that normally affect NSCs in a hypoxic environment. Furthermore, the Lin28/Let-7 pathway may be involved in this regulated function of CDNF. The present study was approved by the Laboratory Animal Centre of Southeast University, China (approval No. 20180924006) on September 24, 2018.
研究领域:
神经科学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Sensors
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2021
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IF 7.711
Wenjun Zhong,Qiufang Yang,Kerui Fang,Dan Xiao,Cuisong Zhou
The simultaneous discrimination of let-7 microRNAs (miRNAs) would greatly facilitate the early diagnosis and prognosis monitoring of diseases. In this work, a molecular beacon DNA probe was designed to be able to flip out its mismatched cytosine base within the α-hemolysin (α-HL) latch and generate completely separated blocking currents to identify the single-base difference. As a result, the characteristic blocking current of fully matched MB/let-7a and single-base mismatched MB/let-7f was 84.30 ± 0.92 and 87.05 ± 0.86% (confidence level P 95%), respectively. Let-7 miRNA family let-7a and let-7f were completely simultaneously discriminated, which could be attributed to the following strengths. (1) The statistic distribution of blocking current is extremely concentrated with a small relative standard deviation (RSD) of less than 1% and a narrow distribution range. (2) Complete separation is achieved with a high separation resolution of 1.54. (3) The cytosine base flipping out within the α-HL latch provides a universal labeling-free strategy to simultaneously discriminate the single-base mismatch. Overall, the target let-7f sequences were detected with a linear range from 0.001 to 10 pM in human serum samples containing 200 nM let-7a. Great potential has been demonstrated for precise detection, early diagnosis, and prognosis monitoring of diseases related to single-base difference.
研究领域:
纳米技术
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生物物理学
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分子生物学
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医学诊断
✓ 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）