SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY
·
2023
·
IF 1.9
Wenchao Pan,Yadong Wang,Caiyan Zhao
Objective To explore the protective effect and related mechanism of miR-140-5p on liver fibrosis by interfering with TGF-β/Smad signaling pathway.Methods Liver fibrosis mice models were established by intraperitoneal injection of CCL4. Hematoxylin and eosin (HE) staining was used to detect the structural and morphological changes of the liver. Masson staining was used to detect collagen deposition. Human hepatic stellate cells (HSCs, LX-2) were transfected with miR-140-5p mimic or inhibitor then treated with TGF-β1. The qRT-PCR and Western blotting was used to detect the expression of related molecules. The luciferase reporter assay was used to identify the target of miR-140-5p.Results Our results indicated that miR-140-5p expression was downregulated in fibrotic liver tissues of model mice and LX-2 cells treated with TGF-β1. The overexpression of miR-140-5p decreased the expression of collagen1(COL1) and α-smooth muscle actin(α-SMA), inhibited the phosphorylation of Smad-2/3 (pSmad-2/3) in LX-2 cells. Conversely, the knockdown of miR-140-5p upregulated COL1 and α-SMA expression, increased Smad-2/3 phosphorylation. A dual-luciferase reporter assay showed that TGFβR1 was a target gene of miR-140-5p. The overexpression of miR-140-5p suppressed TGFβR1 expression in LX-2 cells. Additionally, knockdown of TGFβR1 decreased the expression of COL1 and α-SMA. Conversely, the overexpression of TGFβR1 reversed the inhibitory effect of miR-140-5p upregulation on expression of COL1 and α-SMA.Conclusion miR-140-5p bound to TGFβR1 mRNA 3′-untranslated region(3′UTR) and inhibited the expression of TGFβR1, pSmad-2/3, COL1 and α-SMA, thereby exerting a potential therapeutic effect on hepatic fibrosis.
研究领域:
分子生物学
·
肝病学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Integrative Medicine-JIM
·
2024
·
IF 4.2
Chun-yan Feng,Cheng-song Cai,Xiao-qian Shi,Zhi-juan Zhang,Dan Su,Yun-qing Qiu
Objective Resveratrol (Res) is a promising anticancer drug against hepatocellular carcinoma (HCC), but whether its anti-HCC effects implicate mitophagy remains unclear. Therefore, we aimed to explore the specific role of Res in mitophagy and the related mechanisms during the treatment of HCC. Methods HepG2 cells and tumor-grafted nude mice were used to investigate the effects of low-, middle- and high-dose of Res on HCC progression and mitophagy in vitro and in vivo, respectively. A series of approaches including cell counting kit-8, flow cytometry, wound healing and transwell assays were used to evaluate tumor cell functions. Transmission electron microscopy, immunofluorescence and Western blotting analysis were used to assess mitophagy. Mitochondrial oxygen consumption rate, reactive oxygen species and membrane potential were used to reflect mitochondrial function. After disrupting the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), miR-143-3p, and ribonucleoside reductase M2 (RRM2), the effects of the MALAT1/miR-143-3p/RRM2 axis on cell function and mitophagy under Res treatment were explored in vitro. Additionally, dual-luciferase reporter and chromatin immunoprecipitation were used to confirm interactions between target genes. Results Res significantly inhibited the proliferation and promoted apoptosis of HCC cells in vitro, while significantly suppressing tumor growth in a dose-dependent manner and inducing mitophagy and mitochondrial dysfunction in vivo. Interestingly, MALAT1 was highly expressed in HCC cells and its knockdown upregulated miR-143-3p expression in HCC cells, which subsequently inhibited RRM2 expression. Furthermore, in nude mice grafted with HCC tumors and treated with Res, the expression of MALAT1, miR-143-3p and RRM2 were altered significantly. In vitro data further supported the targeted binding relationships between MALAT1 and miR-143-3p and between miR-143-3p and RRM2. Therefore, a series of cell-based experiments were carried out to study the mechanism of the MALAT1/miR-143-3p/RRM2 axis involved in mitophagy and HCC; these experiments revealed that MALAT1 knockdown, miR-143-3p mimic and RRM silencing potentiated the antitumor effects of Res and its activation of mitophagy. Conclusion Res facilitated mitophagy in HCC and exerted anti-cancer effects by targeting the MALAT1/miR-143-3p/RRM2 axis.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL BIOLOGY INTERNATIONAL
·
2021
·Vol. 45
·期 8
·1710-1719
·
IF 3.612
Yulan Gu,Chuandan Wan,Guoqiang Zhou,Jinlian Zhu,Zhiliang Shi,Zhixiang Zhuang
Gastric cancer (GC) is a kind of malignancy originating from the epithelium of gastric mucosa. Long noncoding RNAs (lncRNAs) are tightly related to the GC progression. Herein, our research was meant to investigate a novel lncRNA thymidylate synthetase opposite strand ( TYMSOS ) in GC. Quantitative real-time polymerase chain reaction was used to analyze TYMSOS expression in GC cells. 5-Ethynyl-2ʹ-deoxyuridine, flow cytometry analysis, and transwell assay detected the influence of TYMSOS on GC cell proliferation, apoptosis, migration, and invasion. Subcellular fractionation and fluorescent in situ hybridization assays determined the cellular localization of TYMSOS in GC cells. Bioinformatics programs, RNA-binding protein immunoprecipitation, RNA pull-down, and luciferase reporter assays measured the molecular interplays of TYMSOS in GC cells. In brief, TYMSOS was highly expressed in GC cells, and TYMSOS silence inhibited GC cell proliferation, migration, and invasion while elevating cell apoptosis. Functionally, TYMSOS functioned as a competing endogenous RNA to posttranscriptionally modulate GC progression. TYMSOS interacted with miR-4739 to regulate its target gene zinc finger protein 703 . Collectively, our study proved the tumor-promoting role of TYMSOS in GC cells, which might offer the utility value for GC treatment.
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
✓ 已验证
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
·
分子生物学
·
分析化学
✓ 已验证
DOI
高影响因子
TISSUE & CELL
·
2021
·
IF 2.466
Jian Wang,Jianming Mo,Yuancai Xie,Chunguang Wang
MiR-216b is ectopically expressed in various cancers. Ultrasound microbubbles (UTMBs) are an effective method for miRNA delivery. This article mainly explored the involvement of lncRNA in the effects of UTMBs-mediated miR-216b on non-small cell lung cancer (NSCLC) progression. Expressions and relationship of miR-216b and MALAT1 were examined using quantitative real-time polymerase chain reaction (qRT-PCR), Pearson , TargetScan, and dual-luciferase reporter assay. After the transfection with liposome- or UTMBs-mediated miR-216b mimic (M) or MALAT1 overexpression plasmid alone or together, levels of miR-216b and MALAT1, cell biological behaviors, as well as expressions of apoptosis- and epithelial mesenchymal transition (EMT)-related markers were examined using qRT-PCR, cell functional experiments, and western blot. Besides, we used qRT-PCR to quantify the expressions of multiple downstream miRNAs of MALAT1. MiR-216b expression was weakened yet MALAT1 expression was enhanced in NSCLC tissues, and miR-216b was negatively bound to MALAT1. TargetScan analysis manifested that miR-216b, targeted by MALAT1, was down-regulated in NSCLC cells. UTMBs-mediated miR-216b M further intensified miR-216b level yet weakened cell biological behaviors. The inhibitory effect of UTMBs-mediated miR-216b M on cell biological behaviors and MALAT1 expression was greatly better relative to that of miR-216b M. Moreover, miR-216b restrained the cell biological behaviors by repressing MALAT1 expression. We further manifested that miR-216b facilitated the expressions of apoptosis-related markers, but restrained those of EMT-related markers by repressing MALAT1 expression. Moreover, UTMBs-mediated miR-216b M enhanced the expressions of downstream multiple miRNAs of MALAT1, but this tendency was reversed by co-transfection of overexpressed MALAT1 and miR-216b M. Collectively, UTMBs-mediated miR-216b M restrained NSCLC cell growth by modulating the MALAT1-miRNA axis.
研究领域:
肿瘤学
·
分子生物学
·
医学超声波技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Translational Oncology
·
2023
·
IF 5
Haibo Liu,Jie Zhang,Jiamin Li,Xiaoying Cao,Kai Yu,Xun Xia,Zongxi Li,Fengbo Wang
Background This study aimed to investigate the specific roles of the long non-coding RNA (lncRNA) proteasome 20S subunit beta 8 ( PSMB8 )-antisense RNA 1 ( AS1 )/microRNA ( miR ) -382–3p /branched-chain amino acid transaminase 1 ( BCAT1 ) interaction network in gliomas. Methods Western blotting and quantitative reverse transcription-polymerase chain reaction were performed to assess the expression levels of lncRNA PSMB8-AS1, BCAT1 , and miR-382-3p . Moreover, the cell proliferation, migration, and apoptosis were assessed using the cell counting kit-8, Transwell, and caspase-3 activity assays, respectively. The biological role of lncRNA PSMB8-AS1 in glioma was investigated in vivo using a xenograft mouse model. Additionally, the associations among lncRNA PSMB8-AS1, miR-382-3p , and BCAT1 were analyzed using dual-luciferase and RNA immunoprecipitation assays and bioinformatics analyses. Results Glioma cell lines and tissues exhibited overexpression of lncRNA PSMB8-AS1 and BCAT1 and low expression of miR-382-3p . Knockdown of PSMB8-AS1 remarkably repressed the tumor growth in vivo and the migration and proliferation of glioma cells in vitro . In contrast, knockdown of lncRNA PSMB8-AS1 increased the cell apoptosis. Mechanistically, PSMB8-AS1 directly targeted miR-382-3p . By sponging miR-382-3p , lncRNA PSMB8-AS1 stimulated the migration and proliferation of glioma cells and suppressed their apoptosis. Additionally, miR-382-3p directly targeted BCAT1 . Inhibition of miR-382-3p reversed the antitumor effects of BCAT1 silencing on glioma progression. Conclusion Our study revealed that lncRNA PSMB8-AS1 aggravated glioma malignancy by enhancing BCAT1 expression after competitively binding to miR-382-3p . Therefore, lncRNA PSMB8-AS1 may be a potential biomarker and therapeutic target for glioma treatment.
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR NEUROSCIENCE
·
2025
·Vol. 76
·期 1
·4
·
IF 2.7
Wu Zhixuan,Wang Dianyi,Yao Jing,Zhang Yue,Liu Jiayu
Background Migraine is a complex neurological disorder. While acupuncture is effective in alleviating migraines, its molecular mechanisms remain unclear. This study aims to explore these mechanisms. Methods We used bioinformatics to identify differentially expressed microRNAs (miRNAs) in migraine patients after acupuncture. Subsequently, luciferase reporter assays were utilized to verify the interaction between miRNAs and their regulated target gene mRNAs. RT-qPCR and Western blot analyzed key miRNAs’ regulatory effects on target genes. We also employed Transwell migration assays and a nitroglycerin (NTG)-induced migraine mouse model to systematically evaluate acupuncture’s efficacy and mechanism. Results Bioinformatics analysis revealed a significant upregulation of Hsa-miR-550a-3-5p in the peripheral blood of migraine patients after acupuncture treatment. Hsa-miR-550a-3-5p could directly inhibit the mRNA and protein expression of platelet and endothelial cell adhesion molecule 1 (PECAM1), reducing nitroglycerin-induced human brain microvascular endothelial cells (HBMECs). Following the downregulation of PECAM1 by hsa-miR-550a-3-5p, the transendothelial migration capacity of monocytes-macrophages was significantly reduced, and reducing the secretion of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6. Furthermore, it alleviates inflammation by regulating M2 macrophage polarization. In NTG-induced mice, acupuncture relieved migraine-like behaviors, an effect abolished by a miR-550a-3-5p inhibitor. Conclusion This study is the first to reveal that after acupuncture treatment, hsa-miR-550a-3-5p can be upregulated to target and inhibit PECAM1, reducing the transendothelial migration of inflammatory cells and the release of inflammatory cytokines, thereby alleviating migraine symptoms. This discovery provides scientific evidence for the efficacy of acupuncture and offers a new target for developing miRNA-based precision treatment strategies.
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2020
·
IF 5.162
Jia-Qi He,Min-Xia Zheng,Hua-Zhong Ying,Yu-Sen Zhong,Huan-Huan Zhang,Min Xu,Chen-Huan Yu
Two polysaccharides (PRP1 and PRP2) were isolated from Platycodonis Radix . Preliminary structural analysis indicated that PRP1 was composed of glucose, fructose, and arabinose in a molar ratio of 1:1.91:1.59 with a molecular weight of 440 kDa, whereas PRP2 was composed of arabinose, fructose, and galactose in a molar ratio of 1:1.39:1.18 with a molecular weight of 2.85 kDa. Compared with PRP2, PRP1 exerted stronger anticancer activity in vitro. Treatment with 5–30 μg/ml of PRP1 significantly inhibited the proliferation of HepG2 cells in vitro, and oral administration at the doses of 75–300 mg/kg also reduced the tumor growth in vivo. The miRNA expression patterns of human liver cancer cells HepG2 in vivo under PRP1 treatment were established, and microRNA-21 (miR-21) as the onco-miRNA was appreciably downregulated. PRP1 repressed the expression of miR-21, which directly targeted and suppressed PTEN (a negative regulator of the PI3K/Akt signaling cascade), and subsequently upregulated the expression of PTEN but downregulated the PI3K/AKT pathway, thereby promoting liver cancer cell apoptosis. These findings indicated that PRP1 inhibited the proliferation and induced the apoptosis of HepG2 mainly via inactivating the miR-21/PI3K/AKT pathway. Therefore, PRP1 could be used as a food supplement and candidate for the treatment of liver cancer.
研究领域:
药理学
·
肿瘤学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Aging-US
·
2021
·
IF 5.682
Jianhao Xu,Liwei Ni,Fenglun Zhao,Xiaoxiao Dai,Jialong Tao,Jia Pan,Aiming Shi,Zhu Shen,Cunjin Su,Yusong Zhang
Background: This study aimed to investigate the aberrant expression of hsa_circ_0002874 in non-small cell lung cancer (NSCLC) and elucidate associated molecular mechanisms that influence apoptosis and induce paclitaxel (PTX) resistance. Methods: Inhibitors were used to downregulate circRNA or miRNA expression. pCDNA plasmid transfection and mimics were used to upregulate circRNA or miRNA expression. Dual-luciferase reporter assays were conducted to evaluate interactions between miR1273f and MDM2. Xenograft tumor models were used to assess the effect of hsa_circ_0002874 and miR1273f on tumor growth. NSCLC tissues and matched non-cancerous tissues were also collected for correlation analysis. Results: hsa_circ_0002874 acts as a sponge for miR1273f which targets MDM2/P53. The stability of the hsa_circ_0002874/miR1273f/MDM2/P53 pathway was verified by upregulating and downregulating the expression of hsa_circ_0002874 and miR1273f. hsa_circ_0002874 downregulation or miR1273f upregulation reversed the resistance of the A549/Taxol cells in xenograft models. The expression of hsa_circ_0002874 was high, and the level of MDM2 was low in NSCLC tissues. P53 was only weakly expressed in NSCLC tissues with high expression of MDM2. Conclusions: hsa_circ_0002874 is strongly expressed in NSCLC tissues and maybe a potential marker for PTX resistance. hsa_circ_0002874 downregulation could regulate miR1273f/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
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2019
·
IF 3.298
Qiaojian Zhang,Shufang Zheng,Shengchen Wang,Wei Wang,Houjuan Xing,Shiwen Xu
Chlorpyrifos (CPF) has become a mainly pollution in water environment. Micro-RNAs (miRNAs) play an important part in the development of apoptosis and autophagy. However, the potential mechanism of CPF induced kidney toxicity and the roles of miRNAs are still unclear. To explore the underlying mechanism, the kidney of common carp exposed to different concentrations of CPF for 40 days was used as a research object. We found that CPF could damage the ultrastructure and function of kidney; and also caused antioxidant system disorder. CPF inhibited the mRNA level of miR-19a which improved AMP-activated protein kinase (AMPK). Furthermore, the detection of apoptosis and autophagy relative genes showed that the expressions of TSC complex subunit 2 (TSC2), light chain 3 (LC3), Dynein, tumor protein 53 (p53), Bcl-2 associated X protein (Bax), caspase-3 and caspase-9 were enhanced and the expressions of nechanistic target of rapamycin (mTOR), Ras homolog mTORC1 binding (Rheb) and B-cell lymphoma (Bcl-2) were reduced in dose-dependent way. Taken together, we conclude that CPF causes oxidative stress and miR-19a-AMPK axis disorder, thereby promotes apoptosis and autophagy in common carp kidney. Our study will provide theoretical basis for toxicology research and environmental protection of CPF.
研究领域:
毒理学
·
环境科学
·
分子生物学
·
水生生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Human Cell
·
2022
·Vol. 35
·期 5
·1577-1590
·
IF 4.374
Hu Yixiang,Zhang Wenyou,Liu Zheng,Xing Qichang,Liu Renzhu,Yan Qingzi,Li Wencan,Liu Xiang
Cervical cancer is one of the most frequent types of cancer in women, which is characterized by high invasion and metastatic tendency in its advanced stage. Emerging evidence indicated that long non-coding RNAs (LncRNAs) are involved in the pathogenesis of cervical cancer. LINC01287 has been reported to play crucial regulatory roles in the pathogenesis and progression of multiple cancers. However, up until now, whether LINC01287 is associated with the initiation and development of cervical cancer remains largely unknown. In the present study, expression levels of LINC01287, miR-513a-5p and stress-associated endoplasmic reticulum protein 1 (SERP1) mRNA were quantified utilizing qRT-PCR. A series of functional experiments including CCK-8 assay, colony formation assay, transwell assay, flow cytometry, and tumor xenograft growth of cervical cancer cells were performed for studying the effects of LINC01287. The luciferase reporter assay, pull-down assay, and western blot were used to confirm the downstream targets of LINC01287 and miR-513a-5p. The results demonstrate that LINC01287 was highly expressed in cervical cancer tissue samples and cell lines. High LINC01287 predicts a poor prognosis for cervical cancer patients. Additional gain- and loss-of-function experiments demonstrated that silencing LINC01287 inhibited cervical cancer cells proliferation, colony formation, migration, apoptosis in vitro and retarded tumor growth and metastasis in vivo. Furthermore, the dual-luciferase reporter gene system and RNA pulldown assay validated that LINC01287 positively regulated SERP1 expressions by sponging miR-513a-5p, and LINC01287 inhibited cervical cancer progression by regulating miR-513a-5p/SERP1 axis. In conclusion, the current study first identified that LINC01287/miR-513a-5p/SERP1 axis played an important role in cervical cancer progression. LINC01287 might be a prognostic biomarker and a target for new therapies in patients with cervical cancer.
研究领域:
肿瘤学
·
分子生物学
·
遗传学
✓ 已验证
DOI
PubMed
高影响因子
Chemical Biology & Drug Design
·
2023
·Vol. 102
·期 1
·101-114
·
IF 3
Meiya Mao,Xiaojiao Zheng,Yuehua Sheng,Jinghan Chai,Huiqing Ding
Evodiamine (EVO) has been demonstrated to promote apoptosis of ovarian cancer cells, and upregulate miR-152-3p level in colorectal cancer. Here, we explore part of the network mechanism of EVO and miR-152-3p in ovarian cancer. The bioinformatics website, dual luciferase reporter assay, and quantitative real-time polymerase chain reaction were applied to analyze the network among EVO, lncRNA, miR-152-3p, and mRNA. The effect and mechanism of EVO on ovarian cancer cells were determined using cell counting kit-8, flow cytometry, TUNEL, Western blot, and rescue experiments. As a result, EVO dose-dependently attenuated cell viability, induced G2/M phase arrest and apoptosis, promoted miR-152-3p level (4.5- or 2-fold changes), and inhibited expressions of NEAT1 (0.225- or 0.367-fold changes), CDK8 (0.625- or 0.571-fold changes), and CDK19 (0.25- or 0.147-fold changes) in OVCAR-3 and SKOV-3 cells. In addition, EVO decreased Bcl-2 expression, but increased the expressions of Bax and c-caspase-3. NEAT1 targeted miR-152-3p which bound to CDK19. The impacts of EVO on cell viability, cycle, apoptosis, and apoptosis-related proteins were partially reversed by miR-152-3p inhibitor, NEAT1 overexpression, or CDK19 overexpression. Furthermore, miR-152-3p mimic offset the effects of NEAT1 or CDK19 overexpression. The role of NEAT1 overexpression in the biological phenotype of ovarian cancer cells was counteracted by shCDK19. In conclusion, EVO attenuates ovarian cancer cell progression via the NEAT1-miR-152-3p-CDK19 axis.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 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）