The lncRNA lnc_AABR07044470.1 promotes the mitochondrial-damaged inflammatory response to neuronal injury via miR-214-3p/PERM1 axis in acute ischemic stroke

Article

作者: Zhao, Shanshan ; Yu, Tao ; Li, Hong ; Wang, Meng ; Wang, Hao ; Wang, Yu ; Qian, Yulin

AbstractPurposeWe investigated the role of lnc_AABR07044470.1 on the occurrence and development of acute ischemic stroke (AIS) and neuronal injury by targeting the miR-214-3p/PERM1 axis to find a novel clinical drug target and prediction and treatment of AIS.MethodsThe mouse AIS animal model was used in vivo experiments and hypoxia/reoxygenation cell model in vitro was established. Firstly, infarction volume and pathological changes of mouse hippocampal neurons were detected using HE staining. Secondly, rat primary neuron apoptosis was detected by flow cytometry assay. The numbers of neuron, microglia and astrocytes were detected using immunofluorescence (IF). Furthermore, binding detection was performed by bioinformatics database and double luciferase reporter assay. Lnc_AABR07044470.1 localization was performed using fluorescence in situ hybridization (FISH).Lnc_AABR07044470.1, miR-214-3pand PERM1mRNA expression was performed using RT-qPCR. NLRP3, ASC, Caspase-1 and PERM1 protein expression was performed using Western blotting. IL-1β was detected by ELISA assay.ResultsMouse four-vessel occlusion could easily establish the animal model, and AIS animal model had an obvious time-dependence. HE staining showed that, compared with the sham group, infarction volume and pathological changes of mouse hippocampal neurons were deteriorated in the model group. Furthermore, compared with the sham group, neurons were significantly reduced, while microglia and astrocytes were significantly activated. Moreover, the bioinformatics prediction and detection of double luciferase reporter confirmed the binding site of lnc_AABR07044470.1 to miR-214-3p and miR-214-3p to Perm1. lnc_AABR07044470.1 and PERM1 expression was significantly down-regulated and miR-214-3pexpression was significantly up-regulated in AIS animal model in vivo. At the same time, the expression of inflammasome NLRP3, ASC, Caspase-1 and pro-inflammatory factor IL-1β was significantly up-regulated in vivo and in vitro. The over-expression of lnc_AABR07044470.1 and miR-214-3p inhibitor could inhibit the neuron apoptosis and the expression of inflammasome NLRP3, ASC, Caspase-1 and pro-inflammatory factor IL-1β and up-regulate the expression of PERM1 in vitro. Finally, over-expression of lnc_AABR07044470.1 and miR-214-3p inhibitor transfected cell model was significant in relieving the AIS and neuronal injury.ConclusionLnc_AABR07044470.1 promotes inflammatory response to neuronal injury via miR-214-3p/PERM1 axis in AIS.

2024-11-01·Pathology - Research and Practice

Circ_0038718 augments colorectal cancer progression through mediating the miR-761/miR-214–3p/ITGA6 axis

Article

作者: Hu, Aixia ; Hu, Jinxing ; Jin, Yuwei ; Li, Daohong ; He, Hui

BACKGROUNDAccumulating studies have disclosed that circular RNAs (circRNAs) are closely associated with the malignant progression of colorectal cancer (CRC). The aim of our work was to reveal the function of circ_0038718 in CRC.METHODSThe level of genes and proteins were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. In vitro researches were executed via utilizing cell counting Kit-8 (CCK-8), EdU, flow cytometry analysis and wound-healing assay, individually. The target relationship was validated by Dual-luciferase reporter assay. In vivo assay was employed through establishing xenograft tumor model.RESULTSCirc_0038718 was identified to be increased in CRC tissues and cells. Circ_0038718 downregulation suppressed cell proliferation, migration and facilitated apoptosis of CRC. Mechanistically, circ_0038718 could sponge miR-761 and miR-214-3p to modulate the expression of ITGA6. The rescue experiments proved that miR-761 or miR-214-3p inhibitor attenuated the repressive impact of circ_0038718 inhibition on CRC cells progression, and overexpressed ITGA6 could weaken the inhibitory effect of miR-761 or miR-214-3p on tumor cells. Furthermore, depletion of circ_0038718 confined the tumor growth in vivo.CONCLUSIONCirc_0038718 aggravated the progression of CRC cells via mediating ITGA6 expression through targeting miR-761 and miR-214-3p, providing a new therapeutic target for CRC patients.

2024-02-01·Biomedicine & Pharmacotherapy

miR-214-3p promotes the pathogenesis of Parkinson's disease by inhibiting autophagy

Article

作者: Yi, Changhua ; Zhang, Jie ; Zhou, Jin ; Gao, Jinghan ; Wang, Xinyu ; Wang, Zhizhong ; Zhang, Mengmeng ; Zhang, Caiyun ; Ma, Xiuchang ; Zhang, Ru ; Dong, Hui ; Qian, Wenxian ; Wang, Wenhui ; Huang, Ping ; Chen, Wei ; Yan, Jiahui ; Zhao, Yunli

Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by dopaminergic neuron death in the substantia nigra, leading to motor dysfunction. Autophagy dysregulation has been implicated in PD pathogenesis. This study explores the role of miR-214-3p in PD, focusing on its impact on autophagy and dopaminergic neuron viability. Using in vitro and in vivo models, we demonstrate that miR-214-3p inhibits autophagy and promotes dopaminergic neuron apoptosis. Behavioral assessments and molecular analyses reveal exacerbation of PD symptoms upon miR-214-3p overexpression. Furthermore, mechanistic investigations identify ATG3 as a target, shedding light on miR-214-3p's regulatory role in autophagy. These findings enhance our understanding of PD pathogenesis and propose miR-214-3p as a potential biomarker and therapeutic target for modulating autophagy and neuronal survival in PD.

项与 Anti-miR-214 相关的新闻（医药）

2023-02-21

·生物谷

J Exp Clin Cancer Res: 肿瘤扩散原因找到了！与间质来源的miR-214相关

肿瘤转移的形成是肿瘤进展最常见的结果，也是导致黑色素瘤和乳腺癌癌症相关死亡的主要原因之一。肿瘤转移的形成是肿瘤进展最常见的结果，也是导致黑色素瘤和乳腺癌癌症相关死亡的主要原因之一。众所周知，转移的形成不仅依赖于肿瘤细胞的特性和行为，而且受到原发肿瘤微环境(TME)中肿瘤与间质细胞之间的串扰，以及肿瘤细胞在渗出过程中在血液循环中的相互作用，以及肿瘤细胞向远处器官扩散时的强烈影响。肿瘤和间质细胞之间的相互作用已经得到了彻底的研究，但整个图景还远未被定义。重要的是，许多研究强调了癌症相关成纤维细胞(CAF)和间充质干细胞(MSCs)在肿瘤扩散中的相关性，并建议将它们作为有效对抗肿瘤进展的治疗靶点。图片来源: https://doi.org/10.1186/s13046-022-02553-5 近日，来自意大利分子生物技术中心的研究者们在J Exp Clin Cancer Res杂志上发表了题为“Stroma-derived miR-214 coordinates tumor dissemination”的文章，该研究发现强调了间质来源的miR-214及其在EVS中的释放与肿瘤扩散的相关性，这为基于miR-214的治疗干预铺平了道路，不仅针对肿瘤细胞，而且针对TME。肿瘤的进展是基于癌细胞和肿瘤微环境(TME)之间的密切相互作用。在本研究中，研究者集中讨论癌症相关成纤维细胞(CAF)、间充质干细胞(MSCs)和microRNAs(MiRs)在乳腺癌和黑色素瘤恶性中所起的作用。研究者使用公共数据库研究了miR-214在原代人类样本间质中的表达，并评估了肿瘤细胞注射后在miR-214高表达(miR-214over)和敲除(miR-214ko)小鼠中的肿瘤形成和扩散。此外，研究者剖析了来自miR-214丰富或枯竭的基质细胞的条件培养液(CM)或细胞外小泡(EV)对细胞转移特性的影响。本研究的证据表明，miR-214在人类癌症或转移样本中的表达主要与间质成分相关，特别是与CAF和MSCs相关。研究者提供的数据显示，在miR-214小鼠体内注射肿瘤细胞会导致更多的渗出和转移形成。同样，用来自miR-214富含间质细胞的CM或EVS处理癌细胞，可增强癌细胞在体外的迁移/侵袭。相反，当来自miR-214缺失的基质细胞的CM或EV用于治疗培养中的细胞时，在miR-214ko小鼠中生长的肿瘤的扩散受到损害，转移特征显著减少。相反，当miR-214ko小鼠被基质来源的富含miR-214的EV预处理时，外渗和转移的形成完全重建。从机制上讲，在IL-6/STAT3信号被激活后，肿瘤细胞能够在基质细胞中诱导miR-214的产生，然后通过EVS释放该信号，随后被癌细胞摄取。在这里，依赖miR-214的促转移程序被激活。 MIR-214在肿瘤-间质细胞相互作用中的作用图片来源: https://doi.org/10.1186/s13046-022-02553-5 总之，研究者展示了肿瘤细胞指示TME细胞产生和存储miR214的能力，miR214随后通过EVS释放到肿瘤细胞，从而激活转移过程。研究者提出了强有力的遗传学证据，表明间质miR-214对于肿瘤的扩散是必不可少的，这与特异性靶向间质miR-214对抗转移形成的相关性有关。（生物谷 Bioon.com）参考文献 Francesca Orso et al. Stroma-derived miR-214 coordinates tumor dissemination. J Exp Clin Cancer Res. 2023 Jan 13;42(1):20. doi: 10.1186/s13046-022-02553-5.