JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2020
·Vol. 24
·期 18
·11001-11011
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IF 4.486
Jun Liu,Jinli Ding,Bing Qu,Jiuying Liu,Xiaojie Song,Qingli Suo,Aifen Zhou,Jing Yang
Polycystic ovary syndrome (PCOS), the most common female endocrine disease that causes anovulatory infertility, still lacks promising strategy for the accurate diagnosis and effective therapeutics of PCOS attributed to its unclear aetiology. In this study, we determined the abnormal reduction in circPSMC3 expression by comparing the ovarian tissue samples of PCOS patients and normal individuals. The symptom relief caused by up-regulation of circPSMC3 in PCOS model mice suggested the potential for further study. In vitro functional experiments confirmed that circPSMC3 can inhibit cell proliferation and promote apoptosis by blocking the cell cycle in human-like granular tumour cell lines. Mechanism study revealed that circPSMC3 may play its role through sponging miR-296-3p to regulate PTEN expression. Collectively, we preliminarily characterized the role and possible insights of circPSMC3/miR-296-3p/PTEN axis in the proliferation and apoptosis of KGN cells. We hope that this work provides some original and valuable information for the research of circRNAs in PCOS, not only to better understand the pathogenesis but also to help provide new clues for seeking for the future therapeutic target of PCOS.
研究领域:
妇科学
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分子生物学
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内分泌学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
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2023
·Vol. 51
·期 6
·1-13
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IF 5.4
Lin Yang,Chun-Feng Cheng,Zhi-Fang Li,Xiao-Jing Huang,Shao-Qing Cai,Shan-Yu Ye,Li-Jun Zhao,Yi Xiong,Dong-Feng Chen,He-Lu Liu,Zhen-Xing Ren,Hong-Cheng Fang
Diabetic cardiomyopathy (DCM) is a cardiovascular disease which has been reported as a major cause of mortality worldwide for several years. Berberine (BBR) is a natural compound extracted from a Chinese herb, with a clinically reported anti‑DCM effect; however, its molecular mechanisms have not yet been fully elucidated. The present study indicated that BBR markedly alleviated DCM by inhibiting IL‑1β secretion and the expression of gasdermin D (Gsdmd) at the post‑transcriptional level. Considering the importance of microRNAs (miRNAs/miRs) in the regulation of the post‑transcriptional process of specific genes, the ability of BBR to upregulate the expression levels of miR‑18a‑3p by activating its promoter (‑1,000/‑500) was examined. Notably, miR‑18a‑3p targeted Gsdmd and abated pyroptosis in high glucose‑treated H9C2 cells. Moreover, miR‑18a‑3p overexpression inhibited Gsdmd expression and improved biomarkers of cardiac function in a rat model of DCM. On the whole, the findings of the present study indicate that BBR alleviates DCM by inhibiting miR‑18a‑3p‑mediated Gsdmd activation; thus, BBR may be considered a potential therapeutic agent for the treatment of DCM.
研究领域:
心脏病学
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药理学
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分子生物学
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糖尿病
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DOI
PubMed
高影响因子
CELL CYCLE
·
2021
·
IF 4.534
Jun Zhu,Qiwei Fu,Jiahua Shao,Jinhui Peng,Qirong Qian,Yiqin Zhou,Yi Chen
This study explored the role of MEG3 in the cartilage differentiation of bone marrow mesenchymal stem cells (BMSCs). We investigated the effects of over-expression and knockdown of MEG3 on cell viability, cell differentiation, and the expressions of MEG3, miR-129-5p, COL2, chondrocyte differentiation-related genes (sry-type high-mobility-group box 9 (SOX9), SOX5, Aggrecan, silent information regulator 1 (SIRT1), and Cartilage oligomeric matrix protein (COMP)). The targeting relationship between MEG3 and miR-129-5p and the target gene of miR-129-5p was confirmed through Starbase, TargetScan and luciferase experiments. Finally, a series of rescue experiments were conducted to study the regulatory effects of MEG3 and miR-129-5p. BMSCs were identified as CD29+ and CD44+ positive, and their differentiation was time-dependent. As BMSCs differentiated, MEG3 expression was up-regulated, but miR-129-5p was down-regulated. Over-expressed MEG3 promoted the viability and differentiation of BMSCs, up-regulated the expressions of COL2 and chondrocyte differentiation-related genes, and inhibited miR-129-5p. Runt-related transcription factor 1 (RUNX1) was negatively regulated as a target gene of miR-129-5p. Results of rescue experiments showed that the inhibitory effect of miR-129-5p mimic on BMSCs could be partially reversed by MEG3. Over-expression of MEG3 regulated the miR-129-5p/RUNX1 axis to promote the differentiation of BMSCs into chondrocytes. This study provides a reliable basis for the application of lncRNA in articular cartilage injury.
研究领域:
干细胞生物学
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分子生物学
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再生医学
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骨科
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DOI
PubMed
高影响因子
Oncology Letters
·
2019
·Vol. 18
·期 4
·3553-3560
·
IF 1.871
Quanliang Li,Shuya Zhang,Mingyu Wang,Shouguang Dong,Yan Wang,Song Liu,Tiancheng Lu,Yuqin Fu,Xiuran Wang,Guihong Chen
Matrine is an alkaloid extracted from the leguminous plant Sophora flavescens. Matrine has clinical effects in the treatment of tumors, including those in lung cancer, nasopharyngeal cancer and liver cancer. However, the effect of matrine on follicular thyroid cancer has not been reported. The aim of the present study was to investigate the effect of matrine on follicular thyroid cancer and its potential mechanism. FTC‑133 follicular thyroid cancer cells were treated with different concentrations of matrine, and an MTT assay showed that matrine inhibited the growth of FTC‑133 cells in a dose‑ and time‑dependent manner with an IC50 value of 154.8 µM. Cell apoptosis was analyzed by flow cytometry and the results showed that matrine effectively induced the apoptosis of FTC‑133 cells. The expression level of microRNA (miR)‑21 was analyzed by reverse transcription‑quantitative PCR (RT‑qPCR) analysis, and the mRNA and protein expression levels of PTEN, Akt and phosphorylated (p)‑Akt were detected by RT‑qPCR analysis and western blotting, respectively. The expression of miR‑21 was significantly downregulated, PTEN was upregulated at the mRNA and protein expression levels, and p‑Akt was downregulated in the FTC‑133 cells. The effects of miR‑21 mimics and miR‑21 inhibitor on the expression of miR‑21, PTEN and Akt in FTC‑133 cells, and the effect of miR‑21 mimics/matrine on the expression of PTEN were also investigated. The results of the present study suggested that matrine inhibited the growth and induced apoptosis of FTC‑133 cells via the miR‑21/PTEN/Akt signaling pathway.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Translational Cancer Research
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2019
·
IF 1.07
Guangyuan Sun,Fei Guo,Xueliang Wu,Lei Han,Jun Xue
Background LncRNA cancer susceptibility candidate 9 (CASC9) is up-regulated in various cancers. In this study, we explored the role of CASC9 in colon cancer (CC). Methods The level of CASC9 in CC tissues, adjacent normal tissues, intestinal epithelial cells (HIEC) and CC cell lines was evaluated by qRT-PCR. HCT116 and SW480 CC cells were transfected with siCASC9. The cell growth and cell proliferation makers (Ki-67 and PCNA) were detected by CCK-8, colony formation and western blotting, respectively. The cell apoptosis and cell cycle were determined by flow cytometry. MicroRNA sponged by CASC9 was predicted by starBase and verified by dual-luciferase reporter assay. Further analyses were performed to investigate the role of CASC9 sponging the microRNA in CC cells by transfection or co-transfection of siCASC9 and miR-145-5p inhibitor. Results LncRNA CASC9 was high-expressed in CC cells and tissues, especially in CC at advanced TNM stages. In HCT116 and SW480 cells, knockdown of CASC9 suppressed cell proliferation, promoted cell apoptosis and arrested cell cycle at G0/G1 phase. Furthermore, CASC9 was observed to sponge and regulate the expression of miR-145-5p, which was down-regulated in CC tissues. Moreover, increased cell proliferation and decreased cell apoptosis and arrested cell cycle caused by miR-145-5p inhibitor were abrogated by the knockdown of CASC9. Conclusions LncRNA CASC9 is an oncogene in CC cells through sponging miR-145-5p. The findings in the current study provide a new understanding on CASC9 in CC.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2021
·
IF 4.432
Liwei Ni,Jianhao Xu,Fenglun Zhao,Xiaoxiao Dai,Jialong Tao,Jie Pan,Aiming Shi,Zhu Shen,Cunjin Su,Yusong Zhang
MicroRNAs (miRNAs) are involved in the initiation and development of cancer and participate in drug resistance. Paclitaxel (PTX) is a first-line chemotherapy drug for advanced non-small cell lung cancer (NSCLC). The abnormal miRNA expression in NSCLC and its association with chemotherapy drug resistance remains largely unknown. The study aimed to investigate the aberrant expression of miR-221–3p in NSCLC and to elucidate its molecular mechanisms in relation to PTX resistance. PTX increased miR-221–3p expression and regulated MDM2/P53 expression in the PTX-sensitive NSCLC strain (A549). Meanwhile, miR-221–3p was rarely expressed and not interfered by PTX in PTX-resistant A549 cells (A549/Taxol). Dual-luciferase reporter assay confirmed that miR-221–3p specifically binds to MDM2 messenger RNA and inhibited MDM2 expression. The expression of MDM2 and P53 showed a negative correlation in NSCLC cell lines. MiR-221–3p down-regulation reduced the sensitivity of A549 cells to PTX, whereas its up-regulation partially reversed the A549/Taxol cells resistance to PTX and increased the chemosensitivity of A549/Taxol cells to PTX in xenograft models. Quantitative polymerase chain reaction analysis revealed that miR-221–3p expression increased, whereas the MDM2 level decreased in human NSCLC tumor tissues. Moreover, Western bolt analysis showed that P53 was lowly expressed in tumor tissues with MDM2 overexpression. Low expression of miR-221–3p in NSCLC tissues might indicate a poor T staging. In conclusion, miR-221–3p overexpression could regulate MDM2/p53 signaling pathway to reverse the PTX resistance of NSCLC and induce apoptosis in vitro and vivo.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2019
·
IF 3.448
Zhaopeng Yan,Bin Zang,Xiaoying Gong,Jiangyue Ren,Rui Wang
Aims Acute pancreatitis (AP) is usually complicated with multiple organ insufficiency, including renal injury. Hyperlipidemia is regarded as a risk factor to induce AP. High-fat diet-induced hyperlipidemic pancreatitis (HP) increased nowadays and showed more severe symptoms and complications than other AP. However, detailed mechanisms or mediators involved in HP complicated with acute renal injury were less studied. Here, we aimed to study how miR-214 expresses in the HP and whether miR-214 has functions to regulate pathological kidney damages induced by HP. Main methods Sprague-Dawley rats were adopted to establish HP model complicated with acute renal injury through long-term high-fat diet and sodium taurocholic injection. Models were injected with LV-rno-miR-214-3p or LV-anti-rno-miR-214-3p to exogenously regulate miR-214-3p to study its impacts on HP via a series of molecular and histological experiments. Key findings MiR-214-3p was found to be up-regulated in the kidney, pancreas and serum of HP rats and also could intensify the pathological alterations, kidney and pancreas damages and fibrosis induced by HP. Inflammatory response in HP was enhanced when miR-214-3p was overexpressed. Besides, miR-214-3p up-regulation was showed to inhibit PTEN expression but increased P-Akt levels in the HP kidney, which might be a possible mechanism to induce severe symptoms of pancreatitis. Knockdown of miR-214-3p showed opposite effects. Significance MiR-214-3p is indicated to exacerbate the tissue damages and inflammatory response caused by HP complicated with acute renal injury, which may provide a novel therapeutic perspective targeting miR-214-3p to treat HP with acute renal injury.
研究领域:
分子生物学
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病理学
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药理学
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DOI
PubMed
高影响因子
TOXICOLOGY
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2024
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IF 4.8
Hong-Yu Fu,Yue Li,Han Cui,Jiu-Zhi Li,Wan-Xue Xu,Xi Wang,Rui-Feng Fan
Mercuric chloride (HgCl 2 ), a widespread environmental pollutant, induces ferroptosis in chicken embryonic kidney (CEK) cells. Whereas activating transcription factor 4 (ATF4), a critical mediator of oxidative homeostasis, plays a dual role in ferroptosis, but its precise mechanisms in HgCl 2 -induced ferroptosis remain elusive. This study aims to investigate the function and molecular mechanism of ATF4 in HgCl 2 -induced ferroptosis. Our results revealed that ATF4 was downregulated during HgCl 2 -induced ferroptosis in CEK cells. Surprisingly, HgCl 2 exposure has no significant impact on ATF4 mRNA level. Further investigation indicated that HgCl 2 enhanced the expression of the E3 ligase beta-transducin repeat-containing protein (β-TrCP) and increased ATF4 ubiquitination. Subsequent findings identified that miR-15b-5p as an upstream modulator of β-TrCP, with miR-15b-5p downregulation observed in HgCl 2 -exposed CEK cells. Importantly, miR-15b-5p mimics suppressed β-TrCP expression and reversed HgCl 2 -induced cellular ferroptosis. Mechanistically, HgCl 2 inhibited miR-15b-5p, and promoted β-TrCP-mediated ubiquitin degradation of ATF4, thereby inhibited the expression of antioxidant-related target genes and promoted ferroptosis. In conclusion, our study highlighted the crucial role of the miR-15b-5p/β-TrCP/ATF4 axis in HgCl 2 -induced nephrotoxicity, offering a new therapeutic target for understanding the mechanism of HgCl 2 nephrotoxicity.
研究领域:
毒理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2025
·
IF 8.4
Wang Hao,Zhang Li,Yang Wan-yue,Ji Xiao-yi,Gao An-qi,Wei Yi-hong,Ding Xin,Kang Yue,Ding Jian-hua,Fan Yi,Lu Ming,Hu Gang
Obesity increases the risk of depression. Evidence shows that peripheral inflammation, glycemic dysregulation, and hyperactivity within the hypothalamic-pituitary-adrenal axis are implicated in both obesity and depression. In this study we investigated the impact of visceral adipose tissue (VAT), a crucial characteristic of obesity, on stress susceptibility in obese mice. Age-matched mice were fed with chow diet (CD) or high-fat diet (HFD), respectively, for 12 weeks. CD mice were deprived of VAT and received transplantation of VAT from HFD mice (TransHFD) or CD mice (TransCD). Extracellular vesicles (EVs) were prepared from VAT of CD or HFD mice, and intravenously injected (100 μg, 4 times in 2 weeks) in naïve mice or injected into hippocampus (5 μg, 4 times in 2 weeks) through implanted bilateral cannula. Depression-like behaviors were assessed 14 days after transplantation. We showed that HFD mice exhibited significantly higher body weight gain and impaired insulin and glucose tolerance, accompanied by increased stress susceptibility. Transplantation of VAT or VAT-derived EVs from HFD mice caused synaptic damage and promoted stress susceptibility in recipient mice. Through inhibiting miRNA biogenesis in the VAT and miRNA sequencing analysis, we demonstrated that miR-140-5p was significantly upregulated in both VAT-EVs and hippocampus of HFD mice. Overexpression of hippocampal miR-140-5p in naïve mice not only facilitated acute stress-induced depression-like behaviors, but also decreased hippocampal CREB-BDNF signaling cascade and synaptic plasticity. Conversely, knockdown of miR-140-5p in the VAT, VAT-EVs or hippocampus of HFD mice protected against acute stress, reducing stress susceptibility that were mediated via CREB-BDNF pathway. In summary, VAT-EVs or the cargo miRNAs in obese mice promote synaptic damage and stress susceptibility, providing potential therapeutic targets for metabolism-related affective disorders.
研究领域:
医学
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神经科学
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分子生物学
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DOI
PubMed
高影响因子
Cancer Cell International
·
2021
·Vol. 21
·期 1
·1-9
·
IF 5.722
Li Li,Zhao Weidong
Background Non-coding RNAs (ncRNAs) have been identified as key regulators during the pathogenesis and development of cancers. However, most of ncRNAs have never been explored in acute myeloid leukemia (AML).Methods Gene expression was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Functional assays were performed to assess the cellular processes in AML cells. The relationship between genes was verified by means of a series of mechanism assays.Results Transmembrane phosphatase with tensin homology pseudogene 1 (TPTEP1) was notably downregulated in AML cells, and functionally acted as a proliferation-inhibitor. Additionally, TPTEP1 suppressed AML cell growth by inactivating c-Jun N-terminal kinase (JNK)/c-JUN signaling pathway. MicroRNA (MiR)-1303, as an oncogene, was predicted and validated as a target of c-JUN in AML cells. Also, TPTEP1 interacted with miR-1303 and they were mutually silenced by each other in AML cells. Furthermore, the effect of TPTEP1 overexpression on AML cell proliferation was counteracted under miR-1303 upregulation.Conclusion Our findings unmasked a feedback loop of TPTEP1/JNK/c-JUN/miR-1303 axis in AML cells, suggesting TPTEP1 and miR-1303 as potential targets for developing therapeutic strategies for AML patients.
研究领域:
分子生物学
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癌症研究
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血液学
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DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2025
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IF 4.6
Qin Ma,Yilong Tu,Wen Yun,Mingming Zhang
A self-driven and self-catalytic (SDSC) tripedal DNA nanomachine was developed for microRNA-21 (miR-21) detection. The microRNA could open one arm of tripedal DNA nanomachine to form DNAzyme with a nearby arm through the proximity effect. After DNAzyme’s cleavage, the exposed DNA arm region competed with the third arm and produced a DNA segment (sequence Q). The released sequence Q initiated the next SDSC cycle of tripedal DNA nanomachine. In the special DNA nanomachines design, the components with close spatial localization were constructed on a single nanostructure, which significantly increased local reactant concentrations and reaction rates. A dynamic correlation was obtained from 10 pM to 50 nM between fluorescence signal and miR-21 concentration. The effective concentration of reactant greatly increased, compared with the free diffusible reactants. Consequently, the incubation time was significantly shorted to 35 min. This strategy showed a promising potential in miRNA detection and disease diagnosis.
研究领域:
生物化学
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分子生物学
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医学诊断
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF NEUROSCIENCE
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2021
·
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.
研究领域:
神经科学
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分子生物学
✓ 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）