BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2018
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IF 2.559
Jianhao Xu,Cunjin Su,Fenglun Zhao,Jialong Tao,Duanmin Hu,Aiming Shi,Jie Pan,Yusong Zhang
Paclitaxel (PTX) is a first-line chemotherapy drug for advanced non-small cell lung cancer (NSCLC). The long-chain non-coding RNA maternally expressed gene 3 (MEG3) is a recognized tumor suppressor . This study aimed to explore the effects of PTX on the expression of MEG3 and its anti-tumor mechanism in lung cancer cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were performed to determine cell proliferation . Quantitative polymerase chain reaction was used to determine the levels of MEG3 expressions. Western blot and immunofluorescence were used to detect protein levels. Small interfering RNA or pCDNA-MEG3 transfection was used to downregulate or upregulate MEG3 expression. Dichlorof luorescein diacetate was used to detect intracellular reactive oxygen species. Flow cytometry was used to analyze apoptosis. PTX significantly inhibited the proliferation of NSCLC cells and increased the expressions of MEG3 and P53. The downregulation of MEG3 attenuated PTX-induced cytotoxicity, whereas upregulation of MEG3 induced cell death and increased P53 expression. The inhibition of P53 caused no effect on the upstream MEG3 expression. Our results suggest that the MEG3-P53 pathway is involved in the apoptosis of A549 cells induced by PTX.
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
GENOMICS
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2021
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IF 5.736
Shiliang Dong,Minrui Ma,Ming Li,Yuexin Guo,Xiaoxiao Zuo,Xiaobin Gu,Mingzhi Zhang,Yonggang Shi
Maternally expressed 3 (MEG3) and RNA binding motif single stranded interacting protein 3 (RBMS3) are abnormally expressed in breast cancer susceptibility genes (BRCA), but the mechanism of the two in breast cancer (BC) is unclear. By performing in vivo and in vitro experiments, we found that MEG3 and RBMS3 were low-expressed, negatively correlated with high-expressed miR-141-3p, were positively correlated with each other in BC. MEG3 targeted miR-141-3p, and miR-141-3p targeted RBMS3. MEG3, which was mainly distributed in BC cytoplasm, could down-regulate miR-141-3p and up-regulate RBMS3, and reverse effect of miR-141-3p on related gene expressions and on promoting cancer development. Overexpressed MEG3 inhibited growth of xenografts, promoted cell apoptosis via regulating apoptosis related factors, and up-regulated RBMS3 expression but down-regulated miR-141-3p. The findings of this study showed that MEG3 inhibited proliferation and promoted apoptosis of BC cells through the miR-141-3p/RBMS3 axis, and MEG3 inhibited growth of xenografts through miR-141-3p.
研究领域:
肿瘤学
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分子生物学
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癌症遗传学
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DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
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2021
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IF 8.071
Jing Li,Xiaojie Quan,Saifei Lei,Gang Chen,Jiawei Hong,Zhenyao Huang,Qi Wang,Weiyi Song,Xinxin Yang
Perfluorooctane sulfonic acid (PFOS) is a persistent environmental pollutant. Exposure to PFOS has been associated with abnormal fetal development. The long non-coding RNA (lncRNA) has been showed to play a role in fetal growth restriction (FGR), preeclampsia (PE) and other pregnancy complications. Whether the lncRNA contributes to PFOS-induced toxicity in the placenta remains unknown. In this study, we investigated the function of lncRNA MEG3 and its derived miR-770 in PFOS-induced placental toxicity. Pregnant mice received gavage administration of different concentrations of PFOS (0.5, 2.5, and 12.5 mg/kg/day) from GD0 to GD17, and HTR-8/SVneo cells were treated with PFOS in the concentrations of 0, 10 −1 , 1, 10 μM. We found that expression levels of miR-770 and its host gene MEG3 were reduced in mice placentas and HTR-8/SVneo cells with exposure of PFOS. A significant hypermethylation was observed at MEG3 promoter in placentas of mice gestational-treated with PFOS. We also confirmed that MEG3 and miR-770 overexpression alleviated the cell growth inhibition induced by PFOS. Furthermore, PTX3 (Pentraxin 3) was identified as the direct target of miR-770 and it was enhanced after PFOS exposure. In summary, our results suggested that MEG3 alleviate PFOS-induced placental cell inhibition through MEG3 /miR-770/ PTX3 axis.
研究领域:
毒理学
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分子生物学
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生殖健康
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DOI
PubMed
高影响因子
ACS Applied Bio Materials
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2020
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IF 0
Hua Yang,Yufei Zhang,Xuan Xu,Huanxiang Wang,Ziyun Huang,Ziling Luo,Xiangxi Deng,Qian Xue,Zhihe Qing,Zhen Zou,Ronghua Yang
Visual imaging of long noncoding RNA (lncRNA) MEG3, a newfound regulator of transactivation and tumor growth suppression, is conducive to unlock the secrets of MEG3 in some important biological processes. Here, for the first time, we designed a DNA tetrahedron-based three-dimensional (3D) catcher for imaging cytoplasmic lncRNA MEG3 in living cells. The 3D catcher is composed of a triple-helix-forming dsDNA with capacity to bind the 5′-end GA-rich domain of the lncRNA MEG3 and four hairpin-shaped antisense sequences toward contiguous domain on MEG3. Once ingested by the cell, the 3D catcher quickly captures lncRNA MEG3 via forming a DNA–RNA triple-helix structure and triggering the hybridization-based string disassembly of the catcher. Concomitantly, the quenched hairpin is opened and the fluorescent signal undergoes lighting on conversion. Ascribed to the triple-helix-induced “domino effect,” the disassembly reaction time is greatly shorter than the reaction with the inability to form a triple helix. The 3D catcher allows detection of long-chain targets as long as 129 nucleotide (129 nt) with a detection limit of 0.36 nM and distinguishes endogenous lncRNA MEG3 fragments in living cells between hepatoma cells and normal hepatocytes, which provides a reliable strategy for monitoring endogenous long fragment nucleic acid biomarkers in early clinical lesion diagnoses.
研究领域:
分子生物学
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医学诊断
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遗传学
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DOI
PubMed
CELL CYCLE
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2021
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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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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2023
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IF 8
Zongguang Tai,Jinyuan Ma,Jianing Ding,Huijun Pan,Rongrong Chai,Congcong Zhu,Zhen Cui,Zhongjian Chen,Quangang Zhu
Purpose The clinical management of patients with castration-resistant prostate cancer (CRPC) is difficult. However, novel treatment methods are gradually being introduced. Considering the adverse effects of traditional treatments, recent studies have investigated gene therapy as a method to combat CRPC; but, the application of long non-coding (lnc) RNA in gene therapy remains scarce, despite their promise. Therefore, it is imperative to develop a system that can efficiently deliver lncRNA for the treatment of CRPC. Here, we investigated the efficacy of a delivery system by introducing the plasmid-encoding tumor suppressor lncRNA MEG3 (pMEG3) in CRPC cells.Materials and Methods An EpDT3 aptamer-linked poly(amidoamine) (PAMAM) dendrimer targeting EpCAM was used to deliver pMEG3 in CRPC cells. The PAMAM-PEG-EpDT3/pMEG3 nanoparticles (NPs) were tested using in vitro cellular assays including cellular uptake, entry, and CCK-8 measurement, and tumor growth inhibition, histological assessment, and safety evaluations in in vivo animal models.Results The EpDT3 aptamer promoted endocytosis of PAMAM and PAMAM-PEG-EpDT3/pMEG3 NPs in CRPC cells. PAMAM-PEG-EpDT3/pMEG3 NPs exhibited a significant anti-CRPC effect, both in vivo and in vitro, when compared to that of unfunctionalized PAMAM-PEG/pMEG3 NPs.Conclusion PAMAM-PEG-EpDT3/pMEG3 NPs can potentially improve gene therapy in CRPC cells.
研究领域:
肿瘤学
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分子生物学
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药学
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基因治疗
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2026
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IF 8.7
Yongchao Jia,Na Li,Haoran Wang,Ronglan Yin,Aobo Shen,Fanhua Zeng,Xueqian Liu,Jiaying Li,Yuanyuan Zhou,Jing Yuan,Ronghuan Yin
MEG3 interacts with ILF3 and downregulates its nuclear protein level. • ILF3 inhibits G. parasuis -induced apoptosis of 3D4/21 cells. • MEG3 scaffolds MDM2 to enhance ILF3 ubiquitination and degradation. • ILF3 binds the anti-apoptotic CFLAR promoter to facilitate its transcription. • MEG3 regulates G. parasuis -induced apoptosis via the MDM2/ILF3/ CFLAR axis. Glaesserella parasuis ( G. parasuis ) is an important opportunistic pathogen that poses a threat to the swine industry, and the induction of host cell apoptosis is one of the key pathogenic mechanisms by which G. parasuis invades and damages the host. Long non-coding RNAs (lncRNAs) exert diverse and crucial biological functions in cells. Maternally expressed gene 3 (MEG3), a lncRNA widely involved in cell proliferation, apoptosis, and immune responses, has been demonstrated to be associated with G. parasuis infection. However, the function and mechanism of MEG3 in regulating G. parasuis -induced apoptosis remain unclear. In this study, we found that in the porcine alveolar macrophage cell line 3D4/21, MEG3 interacts with interleukin enhancer-binding factor 3 (ILF3) and negatively regulates the protein expression of ILF3 in the nucleus. Functional analysis showed that ILF3 suppresses G. parasuis -induced apoptosis of 3D4/21 cells, whereas MEG3 participates in regulating this apoptotic process through its interaction with ILF3. Further mechanistic studies revealed that MEG3 acts as a molecular scaffold to recruit the E3 ubiquitin ligase MDM2, enhances the interaction between MDM2 and ILF3, and thereby promotes the ubiquitination and degradation of ILF3. Moreover, ILF3 binds to the promoter of the anti-apoptotic gene CFLAR to facilitate its transcription, whereas MEG3 inhibits ILF3-mediated transcriptional activation of CFLAR , consequently regulating G. parasuis -induced apoptosis of 3D4/21 cells. This study reveals a novel mechanism by which MEG3 regulates G. parasuis -induced apoptosis of 3D4/21 cells via the MDM2/ILF3/ CFLAR axis. These findings provide new insights into elucidating the molecular pathogenic mechanisms of G. parasuis . Download: Download high-res image (122KB) Download: Download full-size image
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DOI
PubMed
高影响因子
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