Frontiers in Oncology
·
2021
·
IF 6.244
Qin Hongkun,Gui Yanping,Ma Rong,Zhang Heng,Guo Yabing,Ye Yuting,Li Jia,Zhao Li,Wang Yajing
MicroRNAs are a group of endogenous small non-coding RNAs commonly dysregulated in tumorigenesis, including glioblastoma (GBM), the most malignant brain tumor with rapid proliferation, diffuse invasion, and therapeutic resistance. Accumulating evidence has manifested that miR-1258 exerts an inhibitory role in many human cancers. However, the expression pattern of miR-1258 and its potential function in GBM tumorigenesis remain unclear. In this study, we reported that miR-1258 expression decreased with the ascending pathological grade of glioma, which indicated an unfavorable prognosis of patients. Functional assays revealed an inhibitory effect of miR-1258 on malignant proliferation, therapeutic resistance, migration, and invasion of GBM in vitro. Moreover, xenograft models also suggested a repression effect of miR-1258 on gliomagenesis. Mechanistically, miR-1258 directly targeted E2F1 in 3’-untranslated regions and attenuated E2F1-mediated downstream gene PCNA and MMP2 transcriptions. Furthermore, restoration of E2F1 expression in GBM cells effectively rescued the tumor-suppressive effect of miR-1258. Our studies illustrated that miR-1258 functioned as a tumor suppressor in GBM by directly targeting E2F1, subsequently inhibiting PCNA and MMP2 transcriptions, which contributed to new potential targets for GBM therapy and other E2F1-driven cancers.
研究领域:
肿瘤学
·
分子生物学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS TECHNOLOGY
·
2024
·
IF 2.9
Mengcheng Xu,Maolin Zhao
Among deaths related to cardiovascular disease (CVD), arteriosclerosis accounts for three-quarters of the total. The most common treatment for arteriosclerosis is revascularization through the implantation of endovascular scaffolds. However, most metal scaffolds currently available are non-biodegradable, which can lead to rejection reactions. In this study, we have developed a CMCS-PEI/miR polysaccharide nucleic acid nanodrug loaded with miR-199a-5p for the first time. The CMCS-PEI/miR polysaccharide nucleic acid nanodrug exhibits good blood compatibility, successfully transfects cells, and induces apoptosis of vascular endothelial cells. Additionally, PCL/GO composite scaffolds with excellent mechanical properties and biocompatibility were fabricated using 3D printing technology. This technology allows for the customisation of scaffolds to meet the needs of individual patients. The 3D-printed PCL/GO composite scaffolds loaded with CMCS-PEI/miRNA polysaccharide nucleic acid nanodrug effectively induce apoptosis of vascular endothelial cells, showing great potential in promoting the functional repair of arteriosclerosis and preventing vascular restenosis.
研究领域:
心血管疾病
·
生物材料学
·
分子生物学
·
组织工程
✓ 已验证
产品关联
DOI
高影响因子
Experimental and Therapeutic Medicine
·
2019
·Vol. 18
·期 2
·1285-1290
·
IF 1.448
Hanchun Chen,Qiong Lu,Chao Chen,Yunhai Di,Ya'nan Li,Weijie Min,Zhengquan Yu,Dongwei Dai
Mutations of the β‑catenin gene are common in various cancer types. MicroRNA (miR)‑24 suppresses gene expression during the cell cycle. However, the effects of miR‑24 on the cell viability and autophagy of glioma cells, and how these biological processes are regulated by β‑catenin are largely unclear. The current study aimed to investigate the role of β‑catenin in regulating the effects of miR‑24 on the cell viability and autophagy of glioma cells. The expression levels of microtubule‑associated proteins 1A/1B light chain 3B (LC3B) and Beclin1 were detected by immunohistochemistry and western blotting. Glioma C6 cells were transfected with miR‑24 mimics, miR‑24 inhibitors and negative control miRNAs. C6 cells transfected with miR‑24 mimics or negative control miRNAs were treated with the β‑catenin inhibitor, XAV‑939. An MTT assay was utilized to evaluate the viability of C6 cells. The expression of miR‑24 and mRNA expression of autophagy related 4a cysteine peptidase (ATG4A) were detected by quantitative polymerase chain reaction analysis. The protein expression of LC3B and Beclin1 decreased significantly in glioma tissue and glioma C6 cells compared with normal brain tissue. Compared with the negative control group, C6 cells transfected with miR‑24 mimics exhibited significantly higher cell viability at 24 and 48 h, and those transfected with miR‑24 inhibitors exhibited significantly lower cell viability at 48 h. XAV‑939 decreased the stimulatory effects of miR‑24 mimics on the viability of C6 cells. The expression of miR‑24 significantly decreased and ATG4A mRNA significantly increased in C6 cells transfected with XAV‑939 compared with those transfected with the negative control miRNA. XAV‑939 attenuated the miR‑24‑induced decrease of the protein expression of LC3B and Beclin1, and decreased the stimulatory effects of miR‑24 mimics on cell viability. In addition, XAV‑939 attenuated the miR‑24‑induced decrease of autophagy marker expression by attenuating miR‑24 expression and increasing ATG4A mRNA expression in glioma C6 cells. To the best of our knowledge, the present study is the first to demonstrate whether β‑catenin regulates the intracellular effects of miR‑24 on the viability and autophagy of glioma cells. The results also provide some mechanistic basis to the pharmaceutical targeting of WNT signaling in high grade glial tumors.
研究领域:
癌症生物学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
ONCOLOGY REPORTS
·
2019
·Vol. 42
·期 1
·313-320
·
IF 3.041
Xuan‑Chen Tao,Xin‑Yu Zhang,Shi‑Bo Sun,De‑Quan Wu
MicroRNAs (miRNAs) are a class of short noncoding RNAs that negatively regulate gene expression and act as oncogenes or tumor suppressors. Numerous miRNAs have been reported be associated with the occurrence and development of gastric carcinoma (GC). For instance, miR‑92a has been observed to be overexpressed in GC; however, the precise mechanisms underlying the role of miR‑92a in GC and its role in clinical therapy require further investigation. In the present study, it was reported that miR‑92a expression was significantly upregulated in GC tissues compared with in adjacent tissues. Additionally, suppression of miR‑92a significantly reduced SGC7901 cell viability as demonstrated by a Cell Counting Kit‑8 and colony formation assays. Suppression of miR‑92a inhibited SGC7901 cell proliferation as determined by Ki‑67 immunofluorescence staining, and the expression levels of proliferating cell nuclear antigen, cyclin dependent kinase (CDK)4 and CDK6, and increased that of p53. In addition, we reported that suppression of miR‑92a induced apoptosis in SGC7901 cells. Furthermore, bioinformatics analysis identified that ING2 as a potential target of miR‑92a. Downregulation of miR‑92a significantly increased ING2 expression at the mRNA and protein levels. A dual‑luciferase reporter assay validated a direct binding site of miR‑92a on ING2. In addition, SGC7901 cells with suppression of miR‑92a were more sensitive to doxorubicin treatment. Knockdown of miR‑92a reduced the half‑maximal inhibitory concentration of doxorubicin from 147.6 nM to 82.1 nM in SGC7901 cells. Knockdown of miR‑92a also reduced SGC7901 cell survival under doxorubicin stimulation. Furthermore, SGC7901 cells with suppression of miR‑92a harbored a greater number of DNA damage foci upon doxorubicin treatment compared with in control cells. The findings of the present study revealed that miR‑92a contributes to cell proliferation, apoptosis and doxorubicin chemosensitivity in GC cells, which suggests a potential therapeutic strategy for the treatment of GC.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Omega
·
2020
·
IF 2.87
Donghong Liu,Jia Liu,Chao Li,Wei Li,Wei Wang,Jie Liu
Gene therapy is an emerging therapeutic strategy used in clinics. Ultrasound-mediated gene transfection possesses great potential as a secure and available approach for gene delivery. However, transfection efficiency and targeting ability remain challenging. In this study, we developed a kind of ultrasound-aided and targeting nanoparticles for microRNA delivery. These nanoparticles carrying nucleic acids were prepared with cationic poly-(amino acid) encapsulated with perfluoropentane. The formulated nanoparticles were stabilized with negatively charged PGA–PEG–RGD peptide coating. Ultrasound imaging and specific gene transfection using this nanocarrier could be implemented simultaneously. Upon treatment with ultrasound irradiation, phase transition was induced in the nanoparticles and they generated acoustic cavitation, resulting in enhanced gene transfection against the endothelial cells. With the overexpression of miR-181b loaded by the nanoparticles, the TNF-α-stimulated endothelial cells were effectively rescued from the inflammatory state through the protection of cell viability and suppression of cell adhesion.
研究领域:
生物医学工程
·
分子生物学
·
基因治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Reproductive Biology
·
2022
·
IF 2.089
Ai-Xue Chen,Rui-Ying Jin,Wei-Mei Zhou,Yong-Ju Ye,Jia-Li Lu,Yue-Fang Ren,Fei-Lan Xuan
abstract Increasing evidence indicates that circular RNAs (CircRNAs) have an important role in human diseases, including polycystic ovary syndrome (PCOS). Recently, circ_0043533, a novel circRNA, was proposed to be involved in the progression of PCOS. However, its role in PCOS has not been explored. In this study, the expression levels of circ_0043533 and miR-1179 in ovarian granulosa cells (OGCs) were examined by qRT-PCR analysis. Moreover, knockdown of circ_0043533 in OGC lines COV434 and KGN, respectively, the cell viability, proliferation, apoptosis, and cycle-related markers of insulin-triggered OGCs were examined by CCK-8, EdU staining, flow cytometry, and western blot assays, respectively. The interaction between circ_0043533 and miR-1179 was examined by bioinformatics, dual-luciferase assay, and RNA immunoprecipitation. Besides, effects of the miR-1179 inhibitor on cell viability and apoptosis in OGC lines with circ_0043533 knockdown were also evaluated. OGCs and insulin-treated OGCs exhibited higher circ_0043533 levels in comparison to the IOSE80 cells. Additionally, knockdown of circ_0043533 remarkably inhibited the cell viability and proliferation and promoted the apoptosis of insulin-treated COV434 and KGN cells, respectively. Meanwhile, circ_0043533 knockdown could down-regulate the Bcl-2, CDK2, and Cyclin D1 expressions, and up-regulate the Bax levels. Furthermore, we demonstrated that circ_0043533 acted as a sponge to absorb miR-1179. Interestingly, miR-1179 inhibition remarkably attenuated the effect of circ_0043533 silence on cell proliferation and apoptosis in insulin-treated COV434 and KGN cells. Taken together, this study revealed that circ_0043533 knockdown restrained the malignant progression of PCOS via targeting miR-1179. Our data suggested that circ_0043533 would serve as a novel therapeutic target for PCOS.
研究领域:
分子生物学
·
妇科学
·
内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS
·
2025
·
IF 1.3
Jiawei Liang,Chaoqiang Zeng,Wendi Li,Peng Zhou
Glioma represents the prevalent neoplasm type, distinguished by invasive growth and a significant rate of recurrence. This research investigates the prognostic significance and possible molecular mechanisms of miR-551a in gliomas, thereby offering a novel biomarker for gliomas treatment. This study selected 77 glioma patients and 52 craniocerebral injury patients from 2017 to 2023. The expression of miR-551a was assessed by qPCR. The ROC, Cox regression, and KM curve analyses were conducted to evaluate the diagnostic utility and prognostic value of miR-551a. The effects of inhibiting miR-551a on glioma cell functions were evaluated through CCK-8 and transwell assays. miR-551a target genes was conducted by GO and KEGG enrichment analyses, as well as PPI analysis, to elucidate potential gene regulatory relationship. miR-551a exhibited a significant up-regulation in the cerebrospinal fluid of glioma patients (P < 0.001). miR-551a possessed a robust predictive capacity for gliomas (AUC = 0.792, P < 0.001) and serves as a risk factor for unfavorable prognoses (HR = 3.858, P < 0.01), with patients exhibiting low levels of miR-551a showing favorable prognosis (P = 0.004). The inhibition of miR-551a diminished the proliferative (P < 0.05), migratory (P < 0.01), and invasive (P < 0.001) capabilities of glioma cells. miR-551a functioned as an oncogene, with CALM3 identified as critical regulatory targets (P < 0.001). miR-551a is a biological indicator for glioma prediction. It participates in the disease progression of glioma by regulating the functions of glioma cells via CALM3.
研究领域:
生物信息学
·
分子生物学
·
肿瘤学
·
神经病学
·
遗传学
✓ 已验证
DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
·
2025
·
IF 2.9
Zhongming Ye,Qihao Huang,Haipeng Wu,Shimei Wang,Boxin Li,Minjuan Zeng,Tikeng Jiang,Biyan Ye,Yixian Wei,Lei Sun,Shaoying Wang,Yutao Zeng,Yuting Chen,Huanwen Tang
Benzene, a recognized carcinogen, is utilized in synthesizing various chemicals. Epidemiological studies have established a positive correlation between benzene exposure and increased incidences of abnormal menstruation and dysmenorrhea. This exposure might also pose risks to the fetal hematopoietic system. However, the precise molecular mechanisms underlying these effects are not fully understood. In this study, a chronic benzene exposure model was established through dynamic inhalation. We assessed the autophagy levels in mouse ovarian granulosa cells and human ovarian granulosa cells treated with 1,4-benzoquinone using molecular biology techniques such as qPCR, Western blot, and transmission electron microscopy (TEM), etc. The experimental results show that Benzene-exposed mice exhibited autophagy, a reduced number of ovarian granulosa cells, and vacuolar lesions in the fallopian tubes. Cell-based experiments demonstrated that benzene exposure significantly upregulated SNHG15 expression in human ovarian granulosa cells ( P < 0.05). The upregulation of SNHG15 enhanced FOXO3 expression via the miR-3143/FOXO3 axis, which in turn increased the transcription of autophagy-related proteins such as Atg5 ( P < 0.05), ultimately leading to excessive autophagy in granulosa cells and ovarian dysfunction. Benzene and its metabolite benzoquinone increase autophagy in ovarian granulosa cells. The lncRNA SNHG15 regulates this autophagy induced by benzene exposure through sponge-like binding to miR-3143/FOXO3, thus impairing ovarian function. Inhibiting SNHG15, miR-3143, and FOXO3 expression markedly reduced autophagy in granulosa cells and ameliorated ovarian dysfunction resulting from benzene exposure. These results suggest that the ceRNA axis involving SNHG15 may be a potential clinical therapeutic target.
研究领域:
毒理学
·
分子生物学
·
遗传学
·
生殖生物学
·
环境卫生
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Genetics
·
2022
·
IF 4.772
Jiahui Chen,Jiadai Zheng,Nan Zheng,Rui Zhou,Lipin Huang,Jian He,Wenzong Zhu,Riyuan Zhang
Objective: The purpose of this study was to study the role and mechanism of miR-19b-3p in regulating myocardial inflammation and injury of viral myocarditis in viral myocarditis induced by Coxsackievirus B3 (CVB3). A CVB3 infection mouse model was established, the survival rate of mice was recorded after different treatments, cardiac function was detected, the degree of myocardial inflammatory infiltration and injury was detected by immunohistochemical and biochemical analyses, miR-19b-3p and PKNOX1 expression in cardiac tissue and cardiac infiltrating macrophages was detected using RT-PCR, and isolated mouse bone marrow-derived macrophages and the differentiation of macrophages after different transfections were detected. Finally, the binding of miR-19b-3p and PKNOX1 was verified by the dual luciferase reporter gene. The results showed that the expression of miR-19b-3p was significantly downregulated in the cardiac tissue and infiltrating macrophages of CVB3-infected mice, while the expression of PKNOX1 was upregulated. Upregulation of miR-19b-3p has protective effects against CVB3-induced myocardial injury in mice, such as weight gain, prolonged survival, increased left ventricular ejection fraction and left ventricular short axis shortening, reduced inflammation, creatine kinase isoenzyme (CK)-MB, and lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) levels decreased, while interferon-γ and interleukin-6 (IL-6) increased, and the M2/M1 cell ratio was upregulated. In conclusion, miR-19b-3p can regulate macrophage polarization by targeting PKNOX1, and has a protective effect against CVB3-induced inflammation and myocardial injury.
研究领域:
分子生物学
·
心脏病学
·
病毒学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Translational Medicine
·
2024
·Vol. 22
·期 1
·1-19
·
IF 6.1
Xu Haotian,Zheng Yue,Wu Jiaxi,Zhang Ruirui,Zhao Qingyun,Chen Sixian,Peng Wenyi,Cai Dunyu,Gao Yihong,Chen Xingcai,Li Deqing,yuan Shengyi,Li Gang,Nan Aruo
Lung cancer is the primary cause of cancer-related death worldwide, and its global incidence and mortality rates remain high. The differential expression of circular RNAs (circRNAs) can affect the development of cancer, but the mechanisms by which circRNAs regulate lung cancer progression remain unclear. In this study, we identified circSORBS1, a circRNA that has not been previously described in lung cancer and is significantly underexpressed in lung cancer tissues, blood and cell lines, and the low expression of circSORBS1 correlated with tumour grade and prognosis. In vitro and in vivo functional experiments revealed that circSORBS1 overexpression inhibited cell proliferation and migration while enhancing apoptosis. Mechanistically, circSORBS1 acts as a sponge for miR-6779-5p, indirectly inhibiting RUFY3 mRNA degradation. Simultaneously, it binds to RUFY3 mRNA to enhance its stability. This dual regulatory mechanism leads to an increase in RUFY3 protein levels, which ultimately activates the YWHAE/BAD/BCL2 apoptotic signalling pathway and suppresses lung cancer progression. Our findings not only increase the knowledge about the regulatory pattern of circRNA expression but also provide new insights into the mechanisms by which circRNAs regulate lung cancer development.
研究领域:
肿瘤学
·
分子生物学
·
癌症生物学
·
基因组学
✓ 已验证
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2025
·
IF 3.7
Yi-Jun Qi,Ye-Lin Jiao,Pan Chen,Qiao-Qing Zhu,Ran Guo,Dang-Rou Wu,Yu-Bo Du,Wan-Ying Li,Yue-Yue Cheng,Xiao-Shuang Wu,Meng-Xiang Li,Wei Li,Shegan Gao
Porphyromonas gingivalis ( P. gingivalis ), a keystone pathogen in adult periodontitis, is linked to an increased risk of many cancers. Although autophagy stimulated by P. gingivalis in ESCC has been reported, the molecular mechanisms and functional roles of autophagy in P. gingivalis -related ESCC progression are still unclear. P. gingivalis infection promoted the malignant progression of ESCC through autophagy, as demonstrated in both in vitro and in vivo studies. Once P. gingivalis invaded cancer cells, it induced the dephosphorylation and nuclear accumulation of YAP/TAZ, which are the effectors of Hippo pathway. In a TEAD-dependent manner, YAP/TAZ activated the miR-21-5p/RASA1/ERK signaling pathway to enhance autophagy-mediated tumor-promoting roles in the proliferation, migration, and invasion of ESCC. Additionally, P. gingivalis infection was correlated with higher levels of miR-21-5p, YAP/TAZ, and LC3, all of which were associated with shorter overall survival of patients with ESCC. Taken together, our findings reveal that the YAP/TAZ-miR-21-5p-ERK axis plays a crucial role in the P. gingivalis -infected subtype of ESCC, suggesting P. gingivalis and the autophagy pathway as promising therapeutic targets for ESCC treatment.
研究领域:
肿瘤学
·
微生物学
·
分子生物学
·
口腔医学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANTI-CANCER DRUGS
·
2021
·Vol. 33
·期 1
·e145
·
IF 2.248
Liu Dan,Wang Yaya,Li Haiming,Peng Sida,Tan Huo,Huang Zhenqian
Multiple myeloma is a frequent hematologic malignancy. Bortezomib is the first-line drug for multiple myeloma chemotherapy. The present study aimed to investigate the potential role and mechanism of circular RNA chaperonin containing TCP1 subunit 3 (circ-CCT3) in bortezomib resistance of multiple myeloma . The levels of circ-CCT3, microRNA-223-3p ( miR-223-3p ), and bromodomain-containing 4 (BRD4) were detected by quantitative real-time PCR or western blot. Cell Counting Kit-8 (CCK-8) method was used to measure the half-inhibitory concentration of bortezomib and cell viability. Cell cycle distribution, apoptosis, proliferation and migration were determined by flow cytometry, 5-ethynyl-2′-deoxyuridine, and wound healing assay. The levels of relevant proteins were checked via western blot. The binding association between miR-223-3p and circ-CCT3/BRD4 was validated via a dual-luciferase reporter assay. Circ-CCT3 and BRD4 were upregulated, while miR-223-3p was downregulated in bortezomib -resistant multiple myeloma patients and cells. Silencing of circ-CCT3 enhanced the sensitivity of bortezomib -resistant multiple myeloma cells to bortezomib . Circ-CCT3 knockdown weakened bortezomib resistance via modulating miR-223-3p . Moreover, miR-223-3p increased bortezomib sensitivity by inhibiting BRD4. Downregulation of circ-CCT3 attenuated bortezomib resistance of multiple myeloma via regulating miR-223-3p /BRD4 pathway, which provided a new potential target for multiple myeloma chemoresistance.
研究领域:
肿瘤学
·
分子生物学
·
血液学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）