LIFE SCIENCES
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2023
·
IF 6.1
Chenyi Gao,Kunpeng Jia,Jun Fang,Xuan Zhu,Jianming Hu,Yi Zhang,Jinxin Jiang,Xiuyan Yu,Danting Wang,Haochen Gu,Zhigang Chen
Colorectal cancer (CRC) is the second most fatal cancer. Many studies have shown that cancer stemness contributes to resistance to conventional chemotherapy and poor prognosis. However, the mechanisms involved in maintaining cancer stemness in CRC are still obscure and few clinical drugs were used to target cancer stemness. Previous studies had reported CD95 increases the stemness of cancer cells with long-term stimulation of exogenous agonist CD95 ligand (CD95L). However, the expression of CD95L is relative low in many human tumor tissues. In this study, we found that CD95 was highly expressed in CRC cells, and in vitro it promoted the tumorsphere formation, chemotherapy resistance and in vivo tumor growth without stimulation of exogenous CD95L. Mechanistically, the bulk and single-cell RNA-sequencing results suggested that CD95 promotes stemness of CRC cells through upregulation of long non-coding RNAs metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1 ). MALAT1 knockdown inhibited CD95-induced tumorsphere formation and chemotherapy resistance. In summary, our findings reveal that CD95 has the capability to modulate cancer stemness via the action of the lncRNA MALAT1. Targeting CD95 may be a promising strategy to inhibit cancer stemness in CRC.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2021
·
IF 5.858
Xiaodan Tan,Wenjia Guo,Zhe Peng,Chao Gu,Pu Xiang,Yujun Tu,Huizhi Fei,Xia Liu,Yi Lu,Miaomiao Li,Hong Wang,Ying Luo,Junqing Yang
Based on the previous studies, this study was carried out to explore the interaction of LncRNA-Malat1/miR-211-5p in cerebral ischemia reperfusion injury (CIRI). Firstly, the expression changes of LncRNA-MALAT1 and miR-211-5p in ischemia patients’ blood were determined, and the binding sites of them were predicted by bioinformatics. Furthermore, middle cerebral artery occlusion/reperfusion (MCAO/R) injury model was established in adult male SD rats , and primary neuronal oxygen-glucose deprivation/reoxygen-glucose reoxygenation (OGD/R) was established in vitro. The results showed that LncRNA-MALAT1 was significantly up-regulated and miR-211-5p down-regulated in the peripheral blood of patients with ischemic stroke, and the expression changes were negatively correlated. Bioinformatics prediction results showed that LncRNA-MALAT1 had a binding site with miR-211-5p. We also found that LncRNA-Malat1 was significantly up-regulated while miR-211-5p down-regulated in rat cortex tissue and primary neurons treated with OGD/R. In addition, lentivirus interfered with LV-Malat1-RNAi decreased the expression of LncRNA-Malat1 and promoted the up-regulation of miR-211-5p. Combination of LV-Malat1-RNAi and miR-211-5p inhibitor significantly reversed the protective effect of down-regulation of LncRNA-Malat1. Inhibition of LncRNA-Malat1 expression alleviated the neurological deficit score after MCAO/R, improved histopathological damage, and reduced the size of cerebral infarction . Combined administration of LV-Malat1-RNAi + Antagomir-211-5p reversed these effects above. In short, our data suggest that LncRNA-Malat is involved in the occurrence and development of cerebral ischemia reperfusion injury by acting on miR-211-5p and is then regulating the expression of COX-2.
研究领域:
神经科学
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分子生物学
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医学遗传学
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DOI
PubMed
高影响因子
INFLAMMATION
·
2021
·Vol. 44
·期 6
·2580-2591
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IF 4.092
Hu Yubo,Ye Cong,Cheng Shuang,Chen Junyang
Propofol (PPF) is reported to play a protective role in ischemia/reperfusion (I/R) injury, including cerebral ischemia–reperfusion injury (CIRI). This study aims to investigate the mechanism by which PPF ameliorates CIRI. Kunming mice were used to establish the middle cerebral artery occlusion (MCAO)/reperfusion mouse model in vivo. PPF pre-treatment was performed before CIRI. Lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) levels were detected to evaluate the tissue injury. PC12 cells were exposed to hypoxia/reoxygenation (H/R) to construct the in vitro CIRI model, and PC12 cells were pre-treated with PPF before H/R. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect the expression of lncRNA MALAT1 and miR-182-5p. Flow cytometry was used to detect the apoptosis of PC12 cells. Bioinformatics analysis, qRT-PCR, dual-luciferase reporter gene experiments, and RNA immunoprecipitation (RIP) experiments were performed to predict and validate the targeting relationship between MALAT1 and miR-182-5p. Western blot was used to detect Toll-like receptor 4 (TLR4) expression at protein level. PPF pre-treatment remarkably inhibited LDH and CPK levels in the serum of the mice with CIRI, and reduced the apoptosis of PC12 cells exposed to H/R. Besides, PPF pre-treatment markedly suppressed MALAT1 expression in both in vivo and in vitro models and upregulated miR-182-5p expression. MiR-182-5p was validated to be a downstream target gene of MALAT1, and MALAT1 could increase the expression of TLR4 by suppressing miR-182-5p. The effects of PPF on the injury of the mice brain and PC12 cells were partly counteracted by the restoration of MALAT1. PPF protects the brain against I/R-induced injury by regulating MALAT1/miR-182-5p/TLR4 axis.
研究领域:
神经科学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL GENETICS
·
2022
·Vol. 61
·期 3
·916-930
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IF 2.22
Wang Pengwei,Mao Senlin,Yi Tingting,Wang Lihua
Vascular dementia (VaD) is the second most common subtype of dementia, but the precise mechanism underlying VaD is not fully understood. Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) can act as a key regulator in physiological and pathological processes, including neurological disorders, but whether it is correlated with VaD has not been elucidated. In this study, we established a mouse model of VaD by the transient bilateral common carotid artery occlusion surgery. As expected, the Morris water maze showed that VaD mice had significant deficits in spatial learning and memory. MALAT1 was elevated in the hippocampus of VaD mice. Additionally, we found that microRNA (miR)-9-3p was downregulated in the VaD hippocampus. By performing a dual-luciferase report assay, we verified the binding relationship between MALAT1 and miR-9-3p. Interestingly, synapse-associated protein-97 (SAP97), a well-known gene related to synaptic functions, was found upregulated in the hippocampus of VaD mice. In vitro experiments performed on hippocampal neurons demonstrated that miR-9-3p negatively regulated SAP97 expression. The downregulation of MALAT1 in hippocampal neurons increased miR-9-3p and reduced SAP97, whereas miR-9-3p inhibition rescued the MALAT1 downregulation-mediated SAP97 reduction. In conclusion, the present study reported the alterations in the expression levels of MALAT1, miR-9-3p, and SAP97 in the hippocampus of VaD mice, suggesting that MALAT1 targets miR-9-3p to upregulate SAP97 in the hippocampus of mice with VaD. This work will be helpful for understanding the molecular mechanisms of VaD.
研究领域:
神经科学
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分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2024
·Vol. 28
·期 13
·e18527
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IF 4.3
Maomao Miao,Mengying Li,Yunjie Sheng,Peijian Tong,Yang Zhang,Dan Shou
Infected bone defects (IBDs) are the common condition in the clinical practice of orthopaedics. Although surgery and anti-infective medicine are the firstly chosen treatments, in many cases, patients experience a prolonged bone union process after anti-infective treatment. Epimedium-Curculigo herb pair (ECP) has been proved to be effective for bone repair. However, the mechanisms of ECP in IBDs are insufficiency. In this study, Effect of ECP in IBDs was verified by micro-CT and histological examination. Qualitative and quantitative analysis of the main components in ECP containing medicated serum (ECP-CS) were performed. The network pharmacological approaches were then applied to predict potential pathways for ECP associated with bone repair. In addition, the mechanism of ECP regulating LncRNA MALAT1/miRNA-34a-5p/SMAD2 signalling axis was evaluated by molecular biology experiments. In vivo experiments indicated that ECP could significantly promote bone repair. The results of the chemical components analysis and the pathway identification revealed that TGF-β signalling pathway was related to ECP. The results of in vitro experiments indicated that ECP-CS could reverse the damage caused by LPS through inhibiting the expressions of LncRNA MALAT1 and SMAD2, and improving the expressions of miR-34a-5p, ALP, RUNX2 and Collagen type І in osteoblasts significantly. This research showed that ECP could regulate the TGF-β/SMADs signalling pathway to promote bone repair. Meanwhile, ECP could alleviate LPS-induced bone loss by modulating the signalling axis of LncRNA MALAT1/miRNA-34a-5p/ SMAD2 in IBDs.
研究领域:
骨科
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药理学
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分子生物学
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信号转导
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产品关联
DOI
PubMed
高影响因子
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