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lncRNA C2dat1 通过靶向骨肉瘤细胞中的 miR-34a-5p 促进细胞增殖、迁移和侵袭。

lncRNA C2dat1 Promotes Cell Proliferation, Migration, and Invasion by Targeting miR-34a-5p in Osteosarcoma Cells.

机构信息

Department of Emergency Medicine, Jinan Central Hospital, Jinan, Shandong, P.R. China.

Department of Outpatient Service Center, Qianfoshan Hospital of Shandong University, Jinan, Shandong, P.R. China.

出版信息

Oncol Res. 2018 Jun 11;26(5):753-764. doi: 10.3727/096504017X15024946480113. Epub 2017 Aug 15.

Abstract

Osteosarcoma is a highly aggressive malignant bone tumor with poor prognosis. Evidence has suggested that lncRNAs are deregulated in multiple cancers. In this study, we investigated the role of the lncRNA C2dat1 on the biological functions of osteosarcoma cells. The expressions of C2dat1, miR-34a-5p, and Sirt1 in human osteosarcoma cells were altered by transfection with their specific vectors/shRNA or mimic/inhibitor. Cell viability, migration, invasion, and apoptosis were assessed posttransfection. The mRNA and protein levels of C2dat1, miR-34a-5p, and Sirt1 were detected by qRT-PCR and Western blot. The results showed that C2dat1 suppression reduced cell viability, invasion, and migration, whereas it increased cell apoptosis in OS-732 cells. The expression of miR-34a-5p was downregulated when C2dat1 was overexpressed, whereas it negatively regulated Sirt1 expression. miR-34a-5p overexpression inhibited cell viability, migration, and invasion and promoted cell apoptosis in osteosarcoma cells by downregulation of Sirt1. Furthermore, miR-34a-5p overexpression deactivated the p38/ERK/AKT and Wnt/β-catenin signaling pathways by inhibition of Sirt1.

摘要

骨肉瘤是一种预后不良的高度侵袭性恶性骨肿瘤。有证据表明,lncRNAs 在多种癌症中失调。在这项研究中,我们研究了 lncRNA C2dat1 对骨肉瘤细胞生物学功能的作用。通过转染其特定载体/shRNA 或模拟物/抑制剂来改变人骨肉瘤细胞中 C2dat1、miR-34a-5p 和 Sirt1 的表达。转染后评估细胞活力、迁移、侵袭和凋亡。通过 qRT-PCR 和 Western blot 检测 C2dat1、miR-34a-5p 和 Sirt1 的 mRNA 和蛋白水平。结果表明,C2dat1 抑制降低了 OS-732 细胞的活力、侵袭和迁移,而增加了细胞凋亡。C2dat1 过表达时 miR-34a-5p 的表达下调,而 Sirt1 表达受其负调控。miR-34a-5p 通过下调 Sirt1 抑制骨肉瘤细胞活力、迁移和侵袭并促进细胞凋亡。此外,miR-34a-5p 通过抑制 Sirt1 使 p38/ERK/AKT 和 Wnt/β-catenin 信号通路失活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2ac/7844639/c1c3312d9c41/OR-26-753-g001.jpg

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