JOURNAL OF PHARMACY AND PHARMACOLOGY
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2024
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IF 2.8
Gong Enhui,Pan Jiongwei,Ye Zaiting,Cai Xiaoping,Zheng Hao,Yin Zhangyong,Jiang Yiwei,Wang Xin,Cao Zhuo
ObjectivesReportedly, ganoderic acid A (GA-A) increases the sensitivity of hepatocellular carcinoma cells to cisplatin (DDP) chemotherapy. Therefore, this study aims to fathom the influence of GA-A on lung cancer cells.MethodsAfter the construction of A549/DDP cells through exposure to DDP, the effects of GA-A on A549 and A549/DDP cells were revealed by cellular functional assays, western blot and quantitative reverse transcription PCR (qRT-PCR). The DDP-resistant lung cancer tumor was established in vivo, followed by further validation of the mechanism of GA-A.ResultsGA-A suppressed the viability, migration, and invasion while downregulating Beclin and autophagy marker LC3II/LC3I levels and upregulating P62 levels in A549 and A549/DDP cells. These effects were reversed by circFLNA overexpression. Also, GA-A reinforced the sensitivity of A549/DDP cells to DDP, elevated the apoptosis and regulated the circFLNA/miR-486-3p/cytochrome P450 family 1 subfamily A member 1 (CYP1A1)/X-ray repair cross-complementing 1 (XRCC1) axis. The reversal effects of circFLNA overexpression on GA-A-induced viability and apoptosis of A549/DDP cells could all be counteracted in the presence of 3MA. GA-A inhibited lung cancer tumor growth and blocked autophagy.ConclusionGA-A suppresses autophagy by regulating the circFLNA/miR-486-3p/CYP1A1/XRCC1 axis to strengthen the sensitivity of lung cancer cells to DDP.
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Journal of Translational Medicine
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2025
·Vol. 23
·期 1
·1-19
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IF 7.5
Hu Songliu,Zhan Ning,Li Jian,Wang Liqun,Liu Yiyan,Jin Ke,Wang Yixuan,Zhang Juxuan,Chen Yiyang,Bai Yang,Wang Yichong,Qi Lishuang,Liu Shilong
Background Radiotherapy is commonly used for locoregionally advanced NSCLC, but radioresistance is a clinical challenge. The long non-coding RNA CBR3-AS1 mediates radioresistance in NSCLC, yet the underlying molecular mechanism is unclear. This study aims to explore whether and how N6-methyladenosine (m6A) modification regulates CBR3-AS1 expression and promotes NSCLC radioresistance. Methods Integrative bioinformatics analyses were used to investigate the m6A methyltransferases that were associated with CBR3-AS1 expression and radioresistance of patients using data from The Cancer Genome Atlas of lung adenocarcinoma and squamous cell carcinoma. Clinical samples of 133 patients with NSCLC was collected to validate the correlation of the methyltransferase with radioresistance. The functional role and molecular mechanism of the methyltransferase in radioresistance was investigated through a series of in vitro experiments including m6A MeRIP-PCR, lentivirus transfection, RNA immunoprecipitation, Luciferase reporter, Colony formation, Transwell invasion, Flow cytometry, ELISA and TUNEL assay and in vivo experiments. Results The methyltransferase RNA binding motif protein 15 (RBM15) was identified as it was significantly positively correlated with CBR3-AS1 expression and overall survival of NSCLC patients receiving radiotherapy. The clinical samples demonstrated that the high protein expression of RBM15 was significantly enriched in patients with radioresistance as well as associated with poor prognosis of patients receiving radiotherapy. In vitro, RBM15 silencing enhanced the effects of radiation on the growth and invasion inhibition, and apoptosis induction of NSCLC cells; RBM15 overexpression had the opposite effects. Mechanistically, RBM15 induced CBR3-AS1 upregulation via an m6A-IGF2BP3-dependent mechanism, inducing CXCL1 expression by sponging miR-409-3p to recruit myeloid-derived suppressor cells (MDSCs) and inhibit T cell activity. In vivo, RBM15 silencing suppressed MDSC invasiveness and enhanced CD8 + and CD4 + T cell infiltration, causing NSCLC cells to overcome radioresistance. Conclusion Our study identifies methyltransferase RBM15 as a potential therapeutic target for NSCLC radioresistance whose inhibition reverses resistance through limiting MDSC recruitment via the m6A-IGF2BP3-CBR3-AS1/miR-409-3p/CXCL1 axis. Graphical
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Human Cell
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2022
·Vol. 35
·期 5
·1424-1439
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IF 4.374
Liu Wen,Li Guojuan,Li Jing,Chen Wei
The long-term treatment of glucocorticoids is a common cause of osteoporosis (OP). This study concentrated on inquiring into the regulatory role and potential mechanisms of TRG-AS1 on dexamethasone (Dex)-induced OP in rats. We adopted Dex to treat rat osteoblasts and rats to simulate in-vitro and in-vivo OP models, respectively. Gain-of-function assays of TRG-AS1, miR-802 and CAB39 were constructed in rat osteoblasts to make certain the influence of TRG-AS1, miR-802 and CAB39 on differentiation, proliferation and apoptosis of rat osteoblasts. TRG-AS1 and CAB39 were down-regulated in the Dex-induced OP model in rats, in contrast to miR-802. Overexpression of TRG-AS1 restrained Dex-induced inhibition of osteogenic differentiation, promoted CAB39/AMPK/SIRT-1 and inhibited NF-κB, while overexpression of miR-802 bridled the inhibitory effect of TRG-AS1 on OP. miR-802 was targeted by TRG-AS1, and inhibited CAB39. Inhibition of either AMPK or SIRT-1 abated the osteogenic differentiation-promoting effect of CAB39. Animal experiments displayed that overexpressing TRG-AS1 alleviated Dex-induced OP in rats. In conclusion, up-regulation of TRG-AS1 protected against glucocorticoid-induced OP in rats by modulating the miR-802-mediated CAB39/AMPK/SIRT-1/NF-κB axis.
研究领域:
分子生物学
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药理学
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骨科
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CELL CYCLE
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2022
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IF 5.173
Tianjiao Lai,Haifeng Qiu,Lulu Si,Yu Zhen,Danxia Chu,Ruixia Guo
Endometrial carcinoma (EC) originates from the endometrium and is one of the most common tumors in female patients, and its incidence has continued to increase in recent decades. LncRNAs are involved in the pathogenesis and metastasis of a variety of malignant tumors, which indicates that lncRNAs can be used as tumor diagnostic markers and potential therapeutic targets. In this study, we analyzed the RNA transcripts of EC cells from The Cancer Genome Atlas (TCGA) and first reported a novel lncRNA, BMPR1B-AS1, that was more highly expressed in endometrial cancer tissues than in adjacent tissues, and BMPR1B-AS1 could promote endometrial cancer cell proliferation and metastasis. Bioinformatics prediction and experimental results both suggested that BMPR1B-AS1 could modulate the malignant behaviors of endometrial cancer cell lines by sponging miR-7-2-3p to modulate DCLK1, and a DCLK1 inhibitor blocked the activation of the PI3K/Akt/NF-κB signaling pathway. Collectively, this study suggests that the BMPR1B-AS1/miR-7-2-3p/DCLK1 axis contributes to the proliferation and metastasis of endometrial cancer cells via the PI3K/Akt/NF-κB pathway.
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JOURNAL OF NANOBIOTECHNOLOGY
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2022
·Vol. 20
·期 1
·1-20
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IF 9.429
Wu Longlong,Tian Xuan,Zuo Huaiwen,Zheng Weiping,Li Xiang,Yuan Mengshu,Tian Xiaorong,Song Hongli
Background Steatotic livers tolerate ischemia–reperfusion injury (IRI) poorly, increasing the risk of organ dysfunction. Ferroptosis is considered the initiating factor of organ IRI. Heme oxygenase oxygen-1 (HO-1)-modified bone marrow mesenchymal stem cells (BMMSCs) (HO-1/BMMSCs) can reduce hepatic IRI; however, the role of ferroptosis in IRI of steatotic grafts and the effect of HO-1/BMMSCs-derived exosomes (HM-exos) on ferroptosis remain unknown.Methods A model of rat liver transplantation (LT) with a severe steatotic donor liver and a model of hypoxia and reoxygenation (H/R) of steatotic hepatocytes were established. Exosomes were obtained by differential centrifugation, and the differentially expressed genes (DEGs) in liver after HM-exo treatment were detected using RNA sequencing. The expression of ferroptosis markers was analyzed. microRNA (miRNA) sequencing was used to analyze the miRNA profiles in HM-exos.Results We verified the effect of a candidate miRNA on ferroptosis of H/R treated hepatocytes, and observed the effect of exosomes knockout of the candidate miRNA on hepatocytes ferroptosis. In vitro, HM-exo treatment reduced the IRI in steatotic grafts, and enrichment analysis of DEGs suggested that HM-exos were involved in the regulation of the ferroptosis pathway. In vitro, inhibition of ferroptosis by HM-exos reduced hepatocyte injury. HM-exos contained more abundant miR-124-3p, which reduced ferroptosis of H/R-treated cells by inhibiting prostate six transmembrane epithelial antigen 3 (STEAP3), while overexpression of Steap3 reversed the effect of mir-124-3p. In addition, HM-exos from cell knocked out for miR-124-3p showed a weakened inhibitory effect on ferroptosis. Similarly, HM-exo treatment increased the content of miR-124-3p in grafts, while decreasing the level of STEAP3 and reducing the degree of hepatic ferroptosis.Conclusion Ferroptosis is involved in the IRI during LT with a severe steatotic donor liver. miR-124-3p in HM-exos downregulates Steap3 expression to inhibit ferroptosis, thereby attenuating graft IRI, which might be a promising strategy to treat IRI in steatotic grafts.Graphical Abstract
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INTERNATIONAL JOURNAL OF NEUROSCIENCE
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2021
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IF 2.292
Hongyan Wang,Huaiqing Gao
Aim Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique showing improvement effects on Parkinson’s disease (PD). Multiple microRNAs (miRs) are dys-expressed during the progression of PD. In the current study, the potential involvement of miRs in the anti-PD effects of rTMS was explored.Methods PD symptoms were induced in mice with 6-OHDA. The expression profile of miRs influenced by rTMS in PD mice was detected by microarray technique and validated by RT-qPCR detection. The PD mice were treated with rTMS and the changes in cognitive behaviors, substantia nigra neuron number, brain histology, and Aβ1-42 level were detected. The activity of miR-409-3p/PDHB axis was also detected to preliminarily explain the interaction between miRs and rTMS.Results The detection of microarray showed that 266 miRs were dys-expressed in PD mice after the administration of rTMS, including 101 up-regulated ones and 146 down-regulated ones. With validation by RT-qPCR detection, miR-409-3p was selected for subsequent assays. Administrations of rTMS improved cognitive behaviors of mice, increased neuron number, and attenuated brain injuries induced by 6-OHDA. The cerebrospinal fluid (CSF) level of Aβ1-42 was induced, while the brain level of Aβ1-42 was suppressed by rTMS. Regarding miR-409-3p/PDHB axis, rTMS administrations suppressed miR-409-3p level and increased the expression of PDHB.Conclusion Administrations of rTMS showed considerable protective effects on brain tissues against PD-induced injuries, which was associated with the changes in miR levels. The current study demonstrated that the inhibition of miR-409-3p by rTMS contributed to the attenuation of PD by inducing PDHB.
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2019
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IF 2.705
Jinyue Zhu,Weiqing Wang,Xia Wu
Hyperplasia of airway smooth muscle cells (ASMCs) is key to the progression of asthma. Isorhynchophylline (IRN) derived from Uncaria rhynchophylla can inhibit the proliferation of AMSCs. The major purpose of the current study was to assess the effect of IRN on the asthma symptoms was assessed both in vitro and in vivo, and the associated mechanism of the effect was also explored by focusing on the function of miR-200a. Asthma model was induced using ovalbumin (OVA) method and AMSC hyperplasia model was induced using TGF-β1. The effect of IRN on allergic asthma mice and the effect of IRN on the proliferation of ASMCs were investigated as well, and the changes in miR-200a level and FOXC1/NF-κB pathway were detected. The administration of IRN attenuated the eosinophils recruitment in BALF, reduced collagen deposition in lung tissues, and suppressed production of IgE and pro-inflammation cytokines. IRN also inhibited the proliferation and induced the apoptosis of ASMCs. Moreover, the administration of IRN increased the level of miR-200a while inhibited the activation of FOXC1/NF-κB pathway. However, after the inhibition of miR-200a level, the function of IRN on ASMCs was impaired. Collectively, it was demonstrated that the effect of IRN on asthma relied on the up-regulation of miR-200a, which then deactivated FOXC1/NF-κB pathway.
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ENVIRONMENTAL TOXICOLOGY
·
2023
·Vol. 38
·期 11
·2595-2607
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IF 4.5
Jue Wang,Sai Gu,Bo Qin
Background Exosomes are applied as biomarkers in several diseases according to their disease-specific profiles. However, the exosomes effects in functional dyspepsia (FD) are still fragmentary. Here we examined the role of Eosinophil and mast cell derived-exosomes in FD progression. Methods Fifty FD subjects and age- and sex-matched healthy controls were included in this retrospective cohort study. Duodenal mucosa and gastric juice were collected to analyze molecular difference. Eosinophil and mast cell were evaluated by immunofluorescence and microarray was subjected to examine the expression levels of NEAT1, miR-211-5p, and glial cell line-derived neurotrophic factor (GDNF), which were subsequently were tested by quantitative reverse transcription PCR (RT-qPCR) validation cohorts. CCK-8 assays, and wound healing assays were used to evaluate integrity of intestinal mucosal barrier in vitro. Rats' weights and gastric emptying rates were used as evaluation of FD severity in vivo. Results Eosinophil and mast cell were enriched and secreted more exosomes in duodenal mucosa of FD patients. We identified differential lncRNAs that were consistently and significantly up regulated in FD cases. Of these, NEAT1 was further validated by RT-qPCR and had closely relationship with GDNF. MiR-211-5p level was found to be reduced in FD and negatively related with NEAT1 and GDNF. Furthermore, NEAT1and GDNF relived FD while miR-211-5p made symptoms worse. The NEAT1/miR-211-5p/GDNF axis had a good predictive ability for FD. Conclusions The NEAT1/miR-211-5p/GDNF could be a potential FD biomarker.
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IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
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2024
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IF 1.5
Chen Jiye,Chen Jiayao,Li Qinxia,Hu Minxia,Zhong Xingxing,Yu Liang,Zhang Xi,Huang Hongyu,Liu Jing,Huang Ziyi,Liu Xinyi,Xiong Wu
This study aimed to explore the potential of using mesenchymal stem cell (MSC)-derived exosomes (MSC-Exos) pre-treated with Astragaloside IV (ASIV) to alleviate inflammation in high glucose (HG)-damaged endothelial cells. MSC-Exos were isolated from untreated MSCs and ASIV-pre-treated MSCs, and their characteristics were assessed. The expression of miR-146a-5p in MSC-Exos was determined, and it was found that ASIV treatment enhanced its expression. In order to assess the impact of highly miR-146a-5p-expressing MSC-Exos on HG-injured endothelial cells, we established a model of HG-induced inflammation using human umbilical vein endothelial cells (HUVECs). The study measured cell viability, apoptosis, tube formation, and levels of inflammatory cytokines among the different treatment groups. It was found that transferring MSC-Exos with high miR-146a-5p expression to HG-damaged HUVECs increased cell viability and tube formation ability while reducing the number of apoptotic cells. Additionally, changes in inflammatory factors indicated a reduction in the inflammatory response. Further investigation demonstrated that miR-146a-5p inhibited the expression of TNF receptor associated factor 6 (TRAF6) and phosphorylated NF-κB, which are involved in the inflammatory response. This resulted in the alleviation of inflammation in HG-damaged endothelial cells. In summary, our findings indicate that ASIV treatment stimulated the secretion of MSC-Exos that exhibited increased levels of miR-146a-5p. These exosomes, in turn, regulated the TRAF6/NF-κB pathway. As a result of this modulation, the inflammatory response in HG-damaged endothelial cells was alleviated. These findings offer a fresh approach to addressing vascular complications associated with diabetes, which could lead to novel treatment strategies in the field.
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American Journal of Translational Research
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2021
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IF 4.06
Shan Jiang,Chonghe Wang,Jingyao Zhu,Xuezhu Huang
Objective: To investigate the regulatory mechanism of sevoflurane-induced neuronal apoptosis through analyzing the expression of glial cell-derived neurotrophic factor (GDNF) mediated by miR-133, sponged by long non-coding RNA (lncRNA) CDKN2B-AS1. Methods: An in vitro cell injury model was established by using different concentrations of sevoflurane and primary hippocampal neurons. Cell proliferation was detected by Cell Counting Kit-8 (CCK-8); caspase-3 and caspase-9 activities were detected by colorimetry, and apoptotic cells were determined by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Fluorescence in situ hybridization (FISH) analysis was used to detect localized expression of CDKN2B antisense RNA 1 (CDKN2B-AS1), and dual-luciferase reporter assay was employed to verify the correlation of CDKN2B-AS1 and miR-133, and of miR-133 and GDNF. The expression of CDKN2B-AS1, miR-133, and GDNF mRNA in the cell injury model were measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blot was utilized to detect the expression of GDNF protein in the cell injury model. Results: In the cell injury model, CDKN2B-AS1 was highly expressed in the cytoplasm, and CDKN2B-AS1 and GDNF were downregulated and miR-133 was upregulated as detected by qRT-PCR (all P<0.05). The connections between CDKN2B-AS1 and miR-133, and between miR-133 and GDNF were confirmed. That is, CDKN2B-AS1 regulated the expression of GDNF by adsorbing miR-133 (all P<0.05). In cells treated with sevoflurane, overexpression of CDKN2B-AS1 could inhibit caspase-3 and caspase-9 activities and the degree of apoptosis. miR-133 could partially alleviate the effect of overexpressing CDKN2B-AS1 on cells, and si-GDNF the effect of miR-133 inhibitor (all P<0.05). Conclusion: lncRNA CDKN2B-AS1 can up-regulate the expression of GDNF, inhibit neuronal apoptosis, and ease the toxic effect of sevoflurane on neural cells by acting as a sponge to adsorb miR-133.
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BRAIN RESEARCH BULLETIN
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2023
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IF 3.8
Xiao Ji,Zhenwu Zhao
Background Silencing of miR-92a-3p may be beneficial in relieving depression of chronically stressed rats. The level of kruppel-like factor 2 (KLF2) was increased in the striatum of depressed rats after ketamine treatment. Enriched environment (EE) ameliorated depression-like behaviors in rats. However, the specific mechanism of EE treatment on depression induced by chronic unpredictable mild stress (CUMS) remains unclear. Methods After CUMS-induced male Sprague Dawley rats were treated under EE or/and Adeno-Associated Virus (AAV)-miR-92a-3p, depression-like behaviors, cognitive ability, dendritic spine density, as well as levels of miR-92a-3p and KLF2 were detected by the behavioral tests, morris water maze test, Golgi staining, and quantitative real-time polymerase chain reaction (qRT-PCR) as needed. The body weight of rats was also measured. Next, primary hippocampal neurons were cultivated. The targeting relationship between miR-92a-3p and KLF2 was analyzed by TargetScan v7.2 and dual-luciferase reporter assay. After hippocampal neurons were transfected with miR-92a-3p mimic or/and overexpressed KLF2 vector, the cell viability, and apoptosis, together with the levels of KLF2, brain-derived neurotrophic factor (BDNF), phosphorylated (p)-tropomysin related kinase B (p-TrkB) and TrkB were determined by MTT assay, flow cytometry, qRT-PCR, and western blot as needed. Results EE ameliorated CUMS-induced depression-like behaviors and cognitive ability, and elevated the neuronal dendritic spine density and KLF2 level, but reduced miR-92a-3p level in hippocampal tissues, while the above effects were reversed by AAV-miR-92a-3p. MiR-92a-3p mimic restrained cell viability, along with p-TrkB/ TrkB and BDNF levels, but promoted apoptosis in hippocampal neurons, which were reversed by overexpressed KLF2. Conclusion EE ameliorates CUMS-induced depression-like symptoms in rats via regulating the miR-92a-3p/KLF2 pathway.
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MEDICAL SCIENCE MONITOR
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2020
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IF 1.918
Shudong Chen,Chenglei Ren,Hui Zheng,Xianchun Sun,Jundi Dai
Background lncRNA HCP5 plays a cancer-promoting role in a variety of cancers. This study was the first to explore the mechanism of HCP5 in gastric carcinoma (GC). Material/Methods The differences in HCP5 between GC patients and healthy people were revealed in the TCGA database. The expression of HCP5 in GC tissues and adjacent tissues was compared by qRT-PCR. At the same time, the clinic pathological features of the patients were counted. Starbase and luciferase assay predicted and verified that miR-27b-3p is a targeted miRNA for HCP5. The expression of HCP5 and miR-27b-3p in various GC cells was detected by qRT-PCR. Cell viability and metastasis in different treatment groups were assessed by use of Cell Couting Kit-8 assay and clone formation assay, wound-healing assay, and transwell assay. Finally, expression of epithelial-mesenchymal transition (EMT)-associated markers was detected by Western blot. Results We found that HCP5 was overexpressed in GC tissues. Patients with higher expression of HCP5 had larger tumors, were more likely to have lymph node metastasis, and had higher TNM stage. HCP5 was overexpressed in GC cells, but this was reversed by miR-27b-3p. Silencing HCP5 inhibited GC cell viability and metastasis by downregulating Vimentin and N-cadherin and up-regulating E-cadherin, but this effect was partially reversed by miR-27b-3p inhibitor. Conclusions The effect of silencing HCP5 on repressing GC cells viability and metastasis by regulating EMT-associated markers can be partially reversed by miR-27b-3p inhibitor.
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