MOLECULAR PHARMACEUTICS
·
2019
·
IF 4.396
Huanling Guo,Ming Xu,Zhong Cao,Wei Li,Lida Chen,Xiaoyan Xie,Wei Wang,Jie Liu
Ultrasound-induced microbubble sonoporation has been shown to effectively improve drug/gene delivery efficiency by enhancing tissue and cell permeability. However, the microscale size and short duration of ultrasound contrast agents limit their accumulation in target areas. Here, a kind of ultrasound-triggered phase-transitioning and size-changing cationic nanodroplet, perfluoropentane/C9F17-PAsp(DET)/miR-122/poly(glutamic acid)-g-MeO-poly(ethylene glycol) (PGA-g-mPEG) ternary nanodroplets (PFP-TNDs/miR-122), was developed to deliver microRNA-122 (miR-122) for hepatocellular carcinoma (HCC) treatment. PFP served as an ultrasound-sensitive core for ultrasound-triggered phase transition and size change from the nanoscale to the microscale. Positively charged C9F17-PAsp(DET) ensured adequate miRNA loading. PGA-g-mPEG, which served as the shell of the nanodroplet, modified the nanodroplets, enhanced their stability in serum, and protected miR-122 from degradation in vivo. The results exhibited that PFP-TNDs/miR-122 has a nanosize diameter (362 ± 15 nm) and remained stable for 24 h. After treatment with PFP-TNDs/miR-122 combined with ultrasound irradiation, the miR-122 expression level was significantly increased by approximately 600-fold in HepG2 cells, 500-fold in SMMC-7721 cells, and 30-fold in human HCC xenografts. Moreover, PFP-TNDs/miR-122 combined with ultrasound radiation effectively suppressed the growth, migration, and invasion of HCC cells, and inhibited tumor proliferation in mice. This study revealed that the biodegradable PFP-TNDs is a promising therapeutic gene carrier with functions of gene protection and effective gene delivery for clinical applications. Furthermore, PFP-TNDs/miR-122 associated with ultrasound irradiation may pave a new way to improve the prognosis of patients with HCC.
研究领域:
医学
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生物技术
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肿瘤学
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DOI
PubMed
高影响因子
Cancer Nanotechnology
·
2024
·Vol. 15
·期 1
·1-15
·
IF 4.5
Lin Xiuyun,Liu Jie,Wu Guangfeng,Yang Xiu,Yan Wenqiang,Fan Nanfeng,Li Hui
Background Cancer cells can resist chemotherapy through various mechanisms, diminishing treatment outcomes. Research had indicated that combining miR-122 with doxorubicin (DOX) can improve hepatocellular carcinoma (HCC) therapy.Results To explore this, we created a one-pot co-delivery system, Fe-miR-122/DOX, by coordinating miR-122, DOX, and FeII ions into nanoparticles. These nanoparticles display uniform particle sizes, well-defined morphology, and exceptional colloidal stability in 10% FBS and 20% FBS solution over 24 h. When the ratio of DOX to miR-122 was set at 20:1, the loading efficiency of both drugs reached 54.7% and 55.5%, respectively. Cell experiments confirmed that Fe-miR-122/DOX efficiently delivers both miR-122 and DOX, enabling cytoplasmic delivery through lysosomal escape, facilitated by the positive charge of the nanoparticles. Functionally, miR-122 increases intracellular accumulation of DOX by downregulating P-glycoprotein (P-gp) expression, and it promotes apoptosis by downregulating B-cell lymphoma 2 (Bcl-2), which leads to the upregulation of Caspase-3. Additionally, Fe-miR-122/DOX disrupts cIAPs-mediated anti-apoptotic signals, downregulates PARP-1 expression, hinders DNA repair, promotes DNA fragmentation, enhances caspase-3 expression, and triggers programmed cell death, synergistically enhancing its antitumor efficacy. This synergistic mechanism disrupts DNA repair, amplifying DNA damage and apoptosis. Our cytotoxicity and apoptosis assays (with a HepG2 cell apoptosis rate of 85.98%) demonstrated the potent antitumor capability of Fe-miR-122/DOX.Conclusion sThis innovative system has demonstrated good biocompatibility and has the potential to transform HCC therapy. Future research could focus on optimizing the co-delivery system and assessing its efficacy in clinical trials.
研究领域:
肿瘤学
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药理学
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分子生物学
·
纳米技术
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DOI
高影响因子
FASEB JOURNAL
·
2025
·Vol. 39
·期 7
·e70539
·
IF 4.2
Yingjie Shen,Yitong Zhou,Kuziwakwashe Alice Chiwa,Junxin Wang,Shihong Ren,Mingxuan Wang,Hongru Ren,Yeyi Zheng,Ying Yu,Lutao Jiang,Jingmou Yu,Yuchun Qiao,Litai Jin,Jianlin Lou,Xiangkuo Zheng
Psoriasis is an immune-mediated inflammatory dermatological disorder characterized by the interaction between immune cells and keratinocytes, which perpetuates cutaneous inflammation and cellular hyperproliferation. In this study, we identified a strong δ-catenin signature in psoriatic skin; however, the precise role of δ-catenin remains to be elucidated. Additionally, we observed that Interleukin (IL)-17A, a pivotal cytokine involved in the development of psoriatic lesions, induces δ-catenin expression in HEKn and HACAT cells. From a mechanistic perspective, δ-catenin initiated NF-κB signaling, subsequently leading to the activation of IL-6 and IL-8 production. Furthermore, silencing δ-catenin expression mitigated IL-17A-induced hyperproliferation of keratinocytes through the NF-κB pathway. Our study further identified miR-101 and miR-122 as upstream regulators of δ-catenin, exerting their effects by downregulating δ-catenin protein levels. We demonstrated that miR-101 and miR-122 can inhibit the hyperproliferation of keratinocytes induced by δ-catenin. These findings validate the role of δ-catenin in the pathogenesis of psoriasis, particularly in keratinocyte-mediated inflammatory responses and cellular hyperproliferation. Consequently, miR-101 and miR-122 hold potential as therapeutic agents in the treatment of psoriasis. Graphical The schematic diagram delineates the signaling pathway associated with IL-17A-induced psoriasis, highlighting the upregulation of delta-catenin, which initiates NF-κB signaling. This activation subsequently leads to the production of IL-6 and IL-8, as well as the hyperproliferation of keratinocytes. Furthermore, miR-101 and miR-122 function as inhibitors of delta-catenin, effectively obstructing this signaling cascade.
研究领域:
皮肤病学
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分子生物学
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免疫学
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DOI
PubMed
高影响因子
Toxicology Research
·
2015
·Vol. 5
·期 1
·160-167
·
IF 3.983
Liye Zhu,Tao Yu,Xiaozhe Qi,Bo Yang,Lei Shi,Haoshu Luo,Xiaoyun He,Kunlun Huang,Wentao Xu
OTA can induce hepatotoxicity. Our previous research has shown that miRNAs play important roles in the OTA-induced hepatotoxicity. And miR-122 is the most abundant miRNA in the liver and is involved in diverse biological processes. This study was performed to clarify the role of miR-122 in OTA-induced hepatotoxicity. The expression levels of miR-122 and the target genes were quantified by real-time PCR. The OTA-induced apoptosis of hepatocyte and HepG2 cells was evaluated using a TUNEL kit, a CCK-8 kit, a flow cytometer and Hoechst 33342. miR-122 was inhibited in HepG2 cells. The results revealed that OTA affected rat hepatocyte apoptosis. miR-122 decreased at 4 weeks but increased at 13 weeks in the OTA-treated livers, and increased in the OTA-treated HepG2 cells; and the mRNA levels of CCNG1 and Bcl-w increased at 4 weeks and decreased at 13 weeks in the high-dose OTA-treatment groups and decreased in HepG2 cells. The apoptosis of HepG2 cells displayed a dose-related increase with OTA. However, the inhibition of miR-122 greatly reduced OTA-induced apoptosis. p53 decreased in vivo and in vitro. miR-122 is a primary effector of OTA-induced hepatocyte apoptosis through the CCNG1/p53 pathway and Bcl-w/caspase-3 pathway in vivo and in vitro. And miR-122 plays an important role in OTA-induced hepatotoxicity.
研究领域:
分子生物学
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毒理学
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细胞生物学
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DOI
PubMed
高影响因子
BIOCHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 4.446
Ping Ouyang,Yang Qing,Shuhao Zou,Chenxin Fang,Jialun Han,Yuxing Yang,Haiyu Li,Zhencui Wang,Jie Du
It is of great significance to develop a sensitive detection platform for miRNA , a non-invasive biological indicator for the diagnosis, treatment and prognosis monitoring of tumors. In this paper, we design an electrochemical DNA sensor to detect miR-122, based on toehold promoted strand displacement reaction, combined with enzyme assisted cycle amplification. In this strategy, when miR-122 and Exonuclease III (Exo III) coexist in the detection system, the toehold promotes the chain replacement reaction, and the miR-122 hybridizes with a stem-loop DNA, HC-DNA. Simultaneously, Exo III hydrolyzes part of HC-DNA and releases miR-122 and sign-DNA. Then, after multiple enzymatic cyclic amplification reactions (N Cycle), a large amount of Sign-DNA was released. Methylene blue (MB), as the signal molecule, is attached to sign-DNA, close to the surface of the electrode, and resulting in a increased electrochemical signal. Using this method, we can qualitatively analyze the concentration of miR-122 by the amplified electrochemical signals. The detection limit of miR-122 is 0.304 pM, lower than that of the many common large-scale instrumental analysis. Further, the method has good selectivity and anti-interference performance in complex environments. This electrochemical DNA biosensor has potential applications in highly sensitive detection of target molecules even concluding viruses.
研究领域:
生物化学
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分子生物学
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分析化学
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DOI
高影响因子
Frontiers in Immunology
·
2023
·
IF 7.3
Wang Huifang,Li Yichen,Jiang Shuqi,Liu Nan,Zhou Qiuping,Li Qian,Chen Zhuo,Lin Yiyan,Chen Chunbo,Deng Yiyu
Background: Neuroinflammation is a common feature of many neurological diseases, and remains crucial for disease progression and prognosis. Activation of microglia and astrocytes can lead to neuroinflammation. However, little is known about the role of lncRNA xist and miR-122-5p in the pathogenesis of sepsis-associated neuroinflammation (SAN). This study aims to investigate the role of lncRNA xist and miR-122-5p in the pathogenesis of SAN.Methods: Levels of miR-122-5p and proinflammatory mediators were detected in the cerebrospinal fluid (CSF) of patients with intracranial infection (ICI) by ELISA and qRT-PCR. miRNA expression in the periventricular white matter (PWM) in rats was analyzed by high-throughput sequencing. Levels of lncRNA xist, miR-122-5p and proinflammatory mediators in the PWM were measured using qRT-PCR and western blot. Bioinformatics analysis was used to predict the upstream and downstream of miR-122-5p. The interaction between miR-122-5p and its target protein was validated using luciferase reporter assay. BV2 and astrocytes were used to detect the expression of lncRNA xist, miR-122-5p.Results: The level of miR-122-5p was significantly decreased in the CSF of ICI patients, while the expression of IL-1β and TNF-α were significantly upregulated. Furthermore, it was found that the expression of IL-1β and TNF-α were negatively correlated with the level of miR-122-5p. A high-throughput sequencing analysis showed that miR-122-5p expression was downregulated with 1.5-fold changes in the PWM of CLP rats compared with sham group. Bioinformatics analysis found that lncRNA xist and PKCη were the upstream and downstream target genes of miR-122-5p, respectively. The identified lncRNA xist and PKCη were significantly increased in the PWM of CLP rats. Overexpression of miR-122-5p or knockdown of lncRNA xist could significantly downregulate the level of PKCη and proinflammatory mediators from activated microglia and astrocytes. Meanwhile, in vitro investigation showed that silencing lncRNA xist or PKCη or enhancing the expression of miR-122-5p could obviously inhibit the release of proinflammatory mediators in activated BV2 cells and astrocytes.Conclusion: LncRNA xist could regulate microglia and astrocytes activation in the PWM of CLP rats via miR-122-5p/PKCη axis, further mediating sepsis associated neuroinflammation.
研究领域:
神经科学
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炎症学
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分子生物学
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微生物学
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DOI
高影响因子
International Journal of Endocrinology
·
2026
·
IF 2.5
Guoxian Zhu,Lidan Zhang,Wenbao Huang,Jiexia Ding,Lifei Yu,Xiangfei Xu
The aim of this study was to evaluate the effect and mechanism of miR‐122‐5p on hepatic injury induced by hyperthyroidism. Male Sprague Dawley rats were divided into three groups: a normal thyroid function group (sham), a levothyroxine (LT4)–induced hyperthyroidism group (T4 sodium), and a hyperthyroidism group treated with a miR‐122‐5p inhibitor (T4 sodium + antagomir‐122‐5p). Liver tissue pathology, ferroptosis and inflammatory markers, and miR‐122‐5p expression were assessed. Finally, rat hepatocytes (BRL‐3A) were treated with carbon tetrachloride (CCL4) to explore the role of the miR‐122‐5p/CCDC6 axis in hepatocyte injury. We found that miR‐122‐5p was expressed at low levels in liver tissues from hyperthyroid rats. Inhibition of miR‐122‐5p aggravated liver tissue injury. Additionally, in hyperthyroid rats, inflammatory factors, iron content, and markers of ferroptosis were upregulated by miR‐122‐5p inhibitors. Mechanistically, miR‐122‐5p was found to bind to CCDC6 and negatively regulate CCDC6 expression. Furthermore, miR‐122‐5p deletion induced hepatocyte injury by exacerbating the ferroptosis process and mitochondrial damage in CCL4‐treated hepatocytes, a process dependent on CCDC6 expression. The miR‐122‐5p/CCDC6 axis plays a protective role in hyperthyroidism‐induced liver injury and serves as a potential target for the clinical treatment of hyperthyroidism‐associated liver disease.
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DOI
PubMed
高影响因子
METABOLIC BRAIN DISEASE
·
2021
·Vol. 36
·期 7
·2059-2069
·
IF 3.584
Yang Ling,Wang Lijuan,Wang Juan,Liu Ping
Long non-coding RNAs (lncRNAs) play important roles in ischaemic stroke. This study aimed to investigate the role and potential mechanism of lncRNA Gm11974 in ischaemic stroke. Mouse neuroblastoma N2a cells were treated with oxygen–glucose deprivation (OGD). The levels of Gm11974, microRNA-122-5p (miR-122-5p) and semaphorin 3A (SEMA3A) were detected by quantitative real-time PCR (qRT-PCR) or western blot. Cell viability and apoptosis were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, Caspase-3 Assay Kit and flow Cytometry. The levels of oxidative stress indicators were measured by using commercial kits. The relationship between miR-122-5p and Gm11974 or SEMA3A was verified by dual-luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. Middle cerebral artery occlusion (MCAO) in mice was used to mimic ischaemic stroke. Gm11974 and SEMA3A were up-regulated, while miR-122-5p was down-regulated in OGD-treated N2a cells and MCAO mice. Down-regulation of Gm11974 ameliorated OGD-mediated N2a cell damage by increasing cell viability and reducing cell apoptosis and oxidative stress. Gm11974 promoted OGD-induced injury in N2a cells via negatively regulating miR-122-5p. Also, miR-122-5p alleviated OGD-resulted N2a cell injury by targeting SEMA3A. Moreover, silencing of Gm11974 decreased infarct volume and neurological score in MCAO mice. Knockdown of Gm11974 attenuated neuronal injury in ischaemic stroke by regulating miR-122-5p/SEMA3A signaling pathway.
研究领域:
神经科学
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分子生物学
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细胞生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
BIOMARKERS
·
2026
·
IF 1.9
Yang Jiang,Xiaosheng Jin
Background PM2.5-induced COPD lacks effective therapies due to unclear pathogenesis. This study explores the role of miR-122 and PTEN in PM2.5-related COPD.Methods Using a combination of in vitro and in vivo assays, including cigarette smoke extract (CSE)-induced NR8383 cells and a rat smoke model, combined with MTT, qPCR, flow cytometry, WB, HE staining, Masson staining, HIC, and TUNEL assays, we investigated the role of microRNA-122 (miR-122) and phosphatase and tensin homolog (PTEN) in the molecular mechanisms underlying PM2.5-induced COPD.Results Our findings demonstrate that CSE-induced the down-regulated expression of miR-122 leads to the activation of PTEN, which in turn regulates the AKT signaling pathway in NR8383 cells. This modulation results in decreased expression of B-cell lymphoma 2 (BCL2), promoting cell apoptosis. Besides, the result from a rat model of COPD exposed to smoke also confirms this molecular axis which ultimately exacerbating COPD. Specifically, compared with the control, there is significant pulmonary structural damage in model rats exposed to PM2.5, including enlarged alveolar intervals, increased alveolar cavity size, pulmonary fibrosis, and evidence of alveolar destruction with concomitant parabronchial inflammation.Conclusion Our research reveals novel insights of PM2.5-induced COPD and proposes the miR-122/PTEN pathway as a potential therapeutic target.
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DOI
PubMed
高影响因子
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