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载 miR-326 的金纳米颗粒靶向调控肝癌中的 PDK1/AKT/c-myc 轴。

Gold nano-particles (AuNPs) carrying miR-326 targets PDK1/AKT/c-myc axis in hepatocellular carcinoma.

机构信息

a Department of Hepatobiliary Surgery, Gaozhou People's Hospital , Gaozhou , China.

b Department of General Surgery, The First Affiliated Hospital of BaoTou Medical University , Inner Mongolia , China.

出版信息

Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):2830-2837. doi: 10.1080/21691401.2018.1489266.

Abstract

Abnormal expression of microRNAs (miRNAs) contributes to tumour growth and invasion. MiR-326 expression often down-regulates in several kinds of cancer and low expression of miR-326 is linked with poor prognosis in cancer patients. In the present study, we aimed to explore the modulatory mechanism of miR-326 in hepatocellular carcinoma (HCC). miR-326 expression was significantly decreased in HCC cell lines and tissues. miR-326 decreased HCC cell growth by affecting cell-cycle progression and by promoting apoptosis. In addition, miR-326 inhibited HCC cell invasion by decreasing the EMT phenotype. We found that miR-326 functioned as a tumour suppressor by repressing its down-stream target PDK1. C-myc contributed to miR-326 down-regulation through binding at its promoter and inhibited its expression. Based on these results, we conducted a therapeutic experiment by using gold nano-particles (AuNPs) carrying miR-326. Restoration of miR-326 reduced tumour growth . Our findings suggest that miR-326 may be a candidate prognostic biomarker and a target for new therapies in HCC patients.

摘要

异常表达的 microRNAs(miRNAs)会促进肿瘤生长和侵袭。miR-326 在多种癌症中常常下调,其低表达与癌症患者的不良预后相关。在本研究中,我们旨在探索 miR-326 在肝细胞癌(HCC)中的调节机制。miR-326 在 HCC 细胞系和组织中的表达显著降低。miR-326 通过影响细胞周期进程和促进细胞凋亡来降低 HCC 细胞的生长。此外,miR-326 通过降低 EMT 表型抑制 HCC 细胞侵袭。我们发现,miR-326 通过抑制其下游靶标 PDK1 发挥肿瘤抑制作用。C-myc 通过结合其启动子抑制 miR-326 的表达,从而导致 miR-326 下调。基于这些结果,我们使用携带 miR-326 的金纳米粒子(AuNPs)进行了治疗实验。恢复 miR-326 减少了肿瘤生长。我们的研究结果表明,miR-326 可能是 HCC 患者的候选预后生物标志物和新治疗靶点。

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