CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
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2019
·Vol. 47
·期 3
·372-382
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IF 2.336
Ruili Wang,Ying Yang,Hui Wang,Ya He,Chen Li
MicroRNAs (miRNAs) have been shown to have complicated implications in the pathogenesis of Parkinson's disease (PD). However, the role of miR-29c and the underlying mechanism in the development of PD remain not well understood. In this work, the MPTP-treated mice or MPP + -intoxicated SH-SY5Y cells were established as an in vivo or in vitro PD model. Then the specific agomir of miR-29c was employed to examine its biological function on PD progress. We found that miR-29c was down-expressed but SP1 was high-expressed in substantia nigra pars compacta (SNpc) of MPTP-induced PD mice. Overexpression of miR-29c attenuated dopaminergic neuron loss and α-synuclein accumulation in SNpc of PD mice. Furthermore, the increments of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and TUNEL-positive apoptotic cells in MPTP-treated mice were ameliorated by miR-29c. Similarly, in SH-SY5Y cell models of PD, we also found that miR-29c inhibited inflammatory cytokine production, reduced apoptotic rate and suppressed pro-apoptotic regulator activity. In addition, the increased expression of SP1 in PD models was found to be inhibited by miR-29c. Luciferase reporter assay confirmed that SP1 was complementary with miR-29c. Knockdown of SP1 with siRNA restored α-synuclein accumulation, inflammation and apoptosis in MPP + -induced SH-SY5Y cells. Collectively, this current work presents that miR-29c may directly target SP1 to protect against the neuroinflammatory and apoptotic responses in PD, providing a potential biomarker for PD diagnosis and treatment.
研究领域:
神经科学
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分子生物学
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药理学
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Oxidative Medicine and Cellular Longevity
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2022
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IF 7.31
Hongshu Wang,Xianyi Wang,Xiaomin Liu,Jinbao Zhou,Qianqian Yang,Binshu Chai,Yimin Chai,Zhongliang Ma,Shengdi Lu
Diabetes mellitus (DM) is a growing health problem. As a common complication of DM, diabetic foot ulcer (DFU) results in delayed wound healing and is a leading cause of nontraumatic amputation. miR-199a-5p, a short noncoding RNA, had abnormal expression in DFU wound tissues. The expression of miR-199a-5p was significantly increased in DFU wound tissues, skin tissues of diabetic rats, and high glucose-induced cells. Vascular endothelial growth factor A (VEGFA) and Rho-associated kinase 1 (ROCK1) are directly targets of miR-199a-5p. Inhibiting the expression of miR-199a-5p alleviated the inhibition of VEGFA and ROCK1, thereby rescued impaired proliferation and migration of HG-induced cells, and restored the normal function of the cells to some extent. In diabetic rats, inhibition of miR-199a-5p significantly increased the expression of VEGFA and ROCK1, significantly promoted wound healing, and rescued impaired wound healing. miR-199a-5p and its targets showed therapeutic effect on diabetic wounds.
研究领域:
分子生物学
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内分泌学
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伤口愈合
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糖尿病研究
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JOURNAL OF MOLECULAR HISTOLOGY
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2026
·Vol. 57
·期 4
·229
·
IF 2.6
Chen Pei-sheng,Xu Liu-fei,Wang Bo,Zhang Sheng-ping,Luo Yi-yu,Wang Xiang-peng
Glioblastoma (GBM) is a highly malignant brain tumor with a poor prognosis. Long noncoding RNAs (lncRNAs) significantly influence GBM pathogenesis. Although lncRNA MIR4435-2HG is known to promote tumorigenesis in various cancers, its regulatory role in GBM remains undefined. We quantified MIR4435-2HG and miR-181d-5p expression using quantitative reverse transcription polymerase chain reaction. The functional impact of the MIR4435-2HG/miR-181d-5p/MALT1/NF-κB axis was assessed in A172 and U87 MG cells through cell counting kit-8 (CCK-8), wound healing, Transwell, flow cytometry, Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL), western blot, and immunofluorescence assays. Interactions between miR-181d-5p, MIR4435-2HG, and MALT1 were confirmed by dual-luciferase reporter, fluorescence in situ hybridization, RNA immunoprecipitation, and RNA pulldown experiments. Finally, a xenograft tumor model in C57BL/6 mice, combined with hematoxylin and eosin staining, immunohistochemistry, and TUNEL staining, was used to investigate the role of MIR4435-2HG in vivo. The results demonstrated that both MIR4435-2HG and MALT1 were upregulated in GBM tissues and cell lines, whereas the expression of miR-181d-5p was reduced. MIR4435-2HG promoted GBM cell proliferation and metastasis in both in vitro and in vivo experiments. Inhibition of MALT1 reversed the promotive effects of miR-181d-5p knock down on GBM cell proliferation and metastasis. Mechanistic studies revealed that MIR4435-2HG upregulates MALT1 expression and activates the NF-κB signaling pathway by sponging miR-181d-5p. In conclusion, MIR4435-2HG overexpression facilitates the malignant progression of GBM through the miR-181d-5p/MALT1/NF-κB pathway.
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Materials Today Bio
·
2026
·
IF 11
Zeping Yang,Ling Zhang,Zhenlong Wang,Chong Hu,Deqiang Ruan,Fan Zhang,Bin Guo,Yingli Shen,Fu Wang
Cervical cancer is a prevalent form of cancer that affects women on a global scale. MicroRNA-155 (miR-155) has been identified as a key player in cervical cancer, with its over-expression signifying a promising target for therapeutic interventions. However, the molecular mechanisms by which miR-155 contributes to the invasive progression of cervical cancer, as well as miRNA-based therapeutic approaches, remain to be elucidated. To address the issues, we initially investigated the functional role of miR-155 in cervical cancer progression. In vitro and in vivo results demonstrated that miR-155 was closely associated with the malignant progression of cervical cancer through regulation of the epithelial-mesenchymal transition (EMT) process, specifically by directly targeting ZFPM2 protein, thereby exerting oncogenic effects. Based on these findings, we designed manganese-based composite agents, namely MnO 2 @PDA-DNAzyme-substrate-methotrexate nanoparticles (MPDM NPs), for simultaneous miRNA imaging and chemotherapy toward cervical cancer. The MPDM NPs exhibited favorable biocompatibility and tumor microenvironment (TME) responsive release behavior, allowing controlled release of Mn 2+ , methotrexate (MTX), and DNAzyme probes for miR-155 detection and therapeutic intervention. In vivo studies with tumor-bearing mice indicated that the MPDM NPs could effectively target tumors. The Mn 2+ -activate miRNA imaging achieved a detection limit for miR-155 of 0.3 nM. Moreover, the drug MTX enabled tumor chemotherapy by regulating the EMT process. This, in turn, has resulted in an impressive tumor inhibition rate of 86.2%. This proposed strategy indicated significant potential for the advancement of precision theranostics in the context of cervical cancer. Download: Download high-res image (254KB) Download: Download full-size image
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INTERNATIONAL DENTAL JOURNAL
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2026
·Vol. 76
·期 4
·109587
·
IF 5.2
Jingkun Zhang,Li Lin,Huixian Dong,Bingtao Wang,Xiaoshi Chen,Chenhao Wang,Liecong Lin,Jialin Zhong,Guocong Zheng,Qianzhou Jiang
Background The regeneration of functional dentin is a critical clinical goal for preserving tooth vitality after injury, with odontoblastic differentiation of human dental pulp stem cells (hDPSCs) being central to this reparative process. While the long noncoding RNA H19 is recognised as a key regulator of dentin repair, its downstream regulatory network is complex and incompletely mapped. Beyond the previously established H19/miR-140-5p/BMP2 axis, this study identifies a distinct and parallel pathway in which H19 promotes odontoblastic differentiation by downregulating miR-103a-3p, which in turn targets the PIK3R1/AKT and KLF4 signalling cascades. Our findings reveal that these two downstream networks operate independently, further elucidating the multifaceted role of H19 in dentin regeneration. Methodology In this study, we used lentiviral vectors to stably overexpress H19 in hDPSCs. Bioinformatic analysis and dual-luciferase reporter assays were employed to validate the interactions between H19 and miR-103a-3p, as well as between miR-103a-3p and its target mRNAs, including phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) and Kruppel-like factor 4 (KLF4). And qPCR and Western blot were used to investigate the expression pattern of H19 and the potential signalling axis of H19 and key odontogenic markers. Then, alkaline phosphatase and alizarin red S staining were used to evaluate odontogenic differentiation capacity. Finally, a heterotopic pulp regeneration model was established. And HE staining, Masson staining, immunofluorescence and immunohistochemistry were performed to verify the mechanism of H19 regulating odontogenic differentiation in vivo. Results In vitro , H19 promoted odontogenic differentiation of hDPSCs, while miR-103a-3p inhibited them. Both PIK3R1 and KLF4 were identified as direct targets of miR-103a-3p. Ectopic expression of either PIK3R1 or KLF4 restored the odontogenic differentiation capacity of hDPSCs suppressed by miR-103a-3p. Mechanistically, PIK3R1 promoted odontogenesis by activating the PI3K/AKT signalling pathway, whereas KLF4 acted independently as a transcriptional regulator. In vivo , H19 overexpression drove odontoblastic differentiation of hDPSCs by inducing the expression of its downstream targets, PIK3R1 and KLF4. Conclusion Our findings indicated that H19 promoted odontogenic differentiation of hDPSCs by modulating the miR-103a-3p–PIK3R1/AKT and miR-103a-3p–KLF4 axes, underscoring their therapeutic potential for pulp regeneration.
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iScience
·
2026
·Vol. 29
·期 7
·
IF 4.5
Wujin Li,Changjian Lin,Hang Xu,Wenxiang Yue,Yi Xu,Baosong Xie,Daxuan Wang
Sulforaphane (SF) suppresses NSCLC metastasis by modulating miR-616-5p, which is transcriptionally upregulated by the oncogenic transcription factor SPI1. However, the roles of SF, SPI1, and miR-616-5p in NSCLC metastasis remain unclear. In this study, we found that SPI1 expression in NSCLC tissues positively correlated with miR-616-5p levels, and that SPI1 transcriptionally regulated miR-616-5p to promote NSCLC cell invasion and migration. Further analysis showed that SF directly binds SPI1, inhibiting its activity and downregulating miR-616-5p expression, thereby attenuating NSCLC metastasis. However, the poor stability of SF limits its clinical application. To address this, we developed a mesoporous silica nanoparticle (MSN)-based delivery system modified with hyaluronic acid and folic acid (MSNs@SF-HA-FA), which exhibited good stability, enhanced cellular uptake, and improved tumor targeting and anti-metastatic efficacy in NSCLC xenograft models. Collectively, our findings reveal the SPI1/miR-616-5p axis drives NSCLC metastasis and show that MSNs@SF-HA-FA enhances SF′s anti-metastatic effect, highlighting its clinical potential.
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npj Science of Food
·
2026
·
IF 9.7
Shen Linyuan,Ma Jianfeng,Liang Shuang,Yang Yiting,Liao Tianci,Lei Yuhang,Chen Lei,Wang Yan,Zhao Ye,Niu Lili,Gan Mailin,Zhu Li
Diet derived extracellular vesicles (EV) can be absorbed and influence physiological processes. Herein, this study investigates the potential health impacts of extracellular vesicles in meat products. Experimental results showed the extracellular vesicles derived from cooked red meat (RM-EV) and white meat (WM-EV) were successfully isolated via ultra-high speed centrifugation. The median particle size of RM-EV is 137.5 nm and that of WM-EV is 116.1 nm. RM-EV and WM-EV are added to the drinking water of mice for ten weeks. The mice developed insulin resistance and abnormal lipid metabolism in the liver. The influences of RM-EV are more pronounced for mice than WM-EV. High-throughput sequencing indicated that ssc-miR-1 (52.05%) and scc-miR-133a-3p (14.21%) are the most abundant microRNA in RM-EV. However, the highest content of microRNA is gga-miR-133a-3p (44.16%) in WM-EV, followed by gga-miR-1 (21.58%). Therefore, the most abundant ssc-miR-1 in red meat EV (RM-EV-miR-1) was selected for in vitro studies. In vitro experiments revealed that RM-EV-miR-1 inhibited cell proliferation by targeting IGF1 in NCTC1469 liver cell. Besides, RM-EV-miR-1 exacerbates insulin resistance in NCTC1469 insulin resistance cell model by targeting PI3K/AKT signaling pathway. Our findings show that the differential health impacts of red and white meat may be partially attributed to the presence of EV. These results provide novel insights into dietary health from the perspective of EV.
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Scientific Reports
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2026
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IF 4.9
Zhang Yanming,Wu Wenjia,Meng Ting,Yang Shuiping,Miao Gong
This study aimed to investigate the role of miR-25-3p carried by human amnion epithelial cell (hAEC)–derived exosomes in regulating MUC5AC production and apoptosis in conjunctival goblet cells. hAEC-derived exosomes were isolated, characterized, and evaluated for their uptake by conjunctival goblet cells. qRT-PCR, flow cytometry, Western blotting, and ELISA were used to assess the effects of exosomes on MUC5AC expression and apoptosis, with a focus on the contribution of miR-25-3p. The interaction between miR-25-3p and its predicted target BCL2L11 was examined using dual-luciferase reporter assays. Conjunctival goblet cells efficiently internalized hAEC-derived exosomes. Exosome treatment increased MUC5AC expression ( P < 0.01) and reduced apoptosis ( P < 0.01). miR-25-3p was found to mediate these effects, at least in part, through targeting BCL2L11, thereby promoting MUC5AC production ( P < 0.01) and decreasing apoptosis ( P < 0.01). hAEC-derived exosomes, particularly those containing miR-25-3p, modulate mucin expression and apoptosis in conjunctival goblet cells. These findings provide mechanistic insight into how exosomal miRNAs may contribute to maintaining ocular surface homeostasis, suggesting a potential role for exosomal miR-25-3p in supporting ocular surface health.
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MEDICAL ONCOLOGY
·
2026
·Vol. 43
·期 3
·127
·
IF 3.5
Hao Liguo,Yin Qiangqiang,Song Jianing,Yu Xiaoyang,He Jialong,Kang Yu-Ming
In recent studies, circ_0060055, a newly identified circRNA with implications in oncology, was examined for its expression levels in pancreatic cancer cells versus normal pancreatic tissue, utilizing RT-qPCR. This circRNA was evaluated for its effects on cellular functions, including invasion, migration, proliferation, tube formation, vascular leakiness and apoptosis through a series of functional assays, both inhibitory and promotional. Moreover, investigations extended to in vivo studies. Findings suggest a strong association between circ_0060055 and enhanced cellular proliferation, migration, and invasion capabilities, alongside a notable reduction in apoptosis. Alterations in the expression levels of proteins that regulate apoptosis have been observed, characterized by elevated levels of the anti-apoptotic protein Bcl-2 and diminished levels of the pro-apoptotic protein Bax. Additionally, through dual luciferase reporter assays and further qRT-PCR analyses, miR-1298-5p was identified as a direct interactor with circ_0060055, which in turn modulates miR-1298-5p levels, thereby acting as a molecular sponge. The findings highlight the critical influence of circ_0060055 on the progression of pancreatic cancer by regulating essential apoptotic proteins, suggesting it could serve as a potential therapeutic target for pancreatic cancer.
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FOOD RESEARCH INTERNATIONAL
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2026
·
IF 8
Kaili Wang,Xu Zhao,Tong Zhang,Sijia Yang,Sufang Duan,Aili Li,Lu Li
Food allergy (FA) is characterized by an imbalance in T helper cell responses, specifically a dysregulation of the Th17 and Treg cells. While bovine milk exosomes (BMEs) are known to possess immunomodulatory properties, their role in modulating Th17/Treg balance in FA remains unclear. This study aimed to investigate whether BMEs could alleviate FA by restoring Th17/Treg balance and to identify the key miRNA mediators involved, particularly focusing on the STAT signaling pathway. An OVA-sensitized mouse model of FA was established. Mice were treated with varying doses of BMEs. Symptoms, immune parameters, cytokine levels, and relevant signaling pathways were assessed. High-throughput sequencing and bioinformatics were used to identify miRNA candidates. Functional validation was performed using gain- and loss-of-function experiments in splenic lymphocytes. The results showed that BMEs administration significantly alleviated FA symptoms in a dose-dependent manner, restored Th17/Treg balance, and suppressed STAT3/p-STAT3/RORγt activation. High-throughput sequencing revealed miR-320a as a key BME-derived miRNA that targets the STAT pathway. Functional experiments demonstrated that miR-320a overexpression in OVA-sensitized lymphocytes significantly reduced specific antibody production, promoted Treg cell differentiation, and downregulated the STAT3/p-STAT3/RORγt pathway. Conversely, miR-320a knockdown yielded opposing effects, exacerbating the allergic response. BMEs alleviate FA by delivering miR-320a, which targets the STAT3/RORγt axis and corrects Th17/Treg imbalance. These findings reveal a novel cross-species regulatory mechanism of BMEs and support their potential as a natural intervention strategy for FA.
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iScience
·
2024
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IF 4.6
Ke Yang,Shuaining Chai,Helong Song,Sinan Cao,Fangmiao Gao,Chenxuan Zhou,Linwei Li
Esophageal carcinoma (EC) is one of the most common malignant tumors in the world. ECRG4 has been recently discovered to be downregulated in EC. However, the mechanism leading to reduced expression of ECRG4 in esophageal cancer remains obscure. Here, we found that ECRG4 expression was significantly downregulated in EC tissues and cell lines. ECRG4 overexpression led to a significant decrease in proliferation in vitro and in vivo . Mechanistically, ECRG4 can activate IRF3/IFN-γ pathway. IFN-γ can promote the expression of miR-29b. MiR-29b reduces the expression of DNMT1. DNMT1 may affect the expression of ECRG4 by affecting the methylation of ECRG4 promoter. These results reveal ECRG4/IRF3/IFN-γ/miR-29b/DNMT1 positive feedback loop in esophageal carcinoma cells, which may become a potential therapeutic target for esophageal carcinoma.
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EXPERIMENTAL CELL RESEARCH
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2026
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IF 3.5
Ruman Chen,Jiqing He,Na An,Mingzhi Xu,Liheng Wang,Yafei Bai
Background Vascular calcification (VC) is a severe cardiovascular complication of chronic kidney disease (CKD), driven by vascular smooth muscle cell (VSMC) osteogenic trans-differentiation and exacerbated by oxidative stress and cellular dysfunction. Despite its clinical relevance, the molecular mechanisms underlying CKD-associated VC remain incompletely understood. This study investigates the role of Sirtuin 1 (SIRT1) in modulating VC through ferroptosis inhibition and mitophagy activation and examines whether microRNA-181c-5p (miR-181c-5p) contributes to SIRT1 dysregulation in this context. Methods A CKD-associated VC model was induced in rats by 5/6 nephrectomy followed by high calcium/phosphate and calcitriol loading, and an in vitro calcification model was established in primary rat VSMCs. SIRT1 was manipulated using AAV9-mediated overexpression in vivo and plasmid overexpression or inhibition in vitro . Upstream regulation of SIRT1 by miR-181c-5p was predicted bioinformatically and validated by RNA pull-down and dual-luciferase assays. Ferroptosis was assessed by redox and Fe 2+ indices, and mitophagy by Pink1/Parkin, LC3-II and p62 expression. Rescue experiments employed erastin, Mdivi-1 and Parkin knockdown. Results SIRT1 expression was markedly reduced in calcified aortic tissues and VSMCs. SIRT1 overexpression suppressed VC by reducing calcium deposition, downregulating osteogenic markers, and increasing fetuin-A levels. SIRT1 also suppressed ferroptosis by restoring the GSH/GPX4/SLC7A11 axis and limiting ROS and lipid peroxidation, whereas erastin abolished these effects. Mechanistically, miR-181c-5p was found to directly target SIRT1 and promote VSMC calcification by repressing SIRT1. Moreover, SIRT1 promoted mitophagy via the Pink1/Parkin pathway activation. Furthermore, inhibition of mitophagy reversed the anti-ferroptotic effects of SIRT1, confirming their functional interplay. Conclusions SIRT1, negatively regulated by miR-181c-5p, mitigates CKD-associated VC by suppressing ferroptosis and activating Pink1/Parkin-dependent mitophagy in VSMCs, highlighting a potential therapeutic axis for vascular protection in CKD. Clinical trial registration number Not applicable.
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