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长链非编码 RNA PVT1 通过靶向 miR-378c 调控 SLC2A1 表达促进肺腺癌细胞的侵袭生长。

The lncRNA PVT1 promotes invasive growth of lung adenocarcinoma cells by targeting miR-378c to regulate SLC2A1 expression.

机构信息

Department of Thoracic, Qingpu Branch of Zhongshan Hospital Affiliated To Fudan University, Shanghai, 201700, China.

Department of Peditrict, Qingpu Branch of Zhongshan Hospital Affiliated To Fudan University, No. 1158, East Park Road, Qingpu District, Shanghai, 201700, China.

出版信息

Hum Cell. 2021 Jan;34(1):201-210. doi: 10.1007/s13577-020-00434-7. Epub 2020 Sep 22.

Abstract

As an oncogene, plasmacytoma variant translocation 1 (PVT1) has been found to be highly expressed in several cancers. However, its specific role in lung adenocarcinoma (ADC) has not been fully elucidated. In this study, the expression of PVT1, miR-378c, and solute carrier family 2 member 1 (SLC2A1) was determined by quantitative real-time PCR and western blot. Dual-luciferase reporter assay was used to explore the relationship between PVT1 and miR-378c, as well as miR-378c and SLC2A1. The effects of PVT1 on the lung ADC cells proliferation, invasion, and migration were detected using MTT, wound-healing, and transwell assays. The results revealed that PVT1 was highly expressed in lung ADC cells, and the overexpression of PVT1 promoted the proliferation, migration, and invasion of lung ADC cells. In lung ADC cells, PVT1 negatively regulated miR-378c expression, and miR-378c negatively regulated SLC2A1 expression through binding to its 3'-untranslated coding regions. Knocking down of PVT1 inhibited the abilities of cell proliferation, migration, and invasion, while miR-378c inhibitor or SLC2A1 Vector diminished the effect. Together, silencing PVT1 downregulated SLC2A1 expression via targeting miR-378c, and then repressed lung ADC cells growth, migration, and invasion.

摘要

作为一种癌基因,浆细胞瘤变异易位 1(PVT1)已被发现高表达于多种癌症中。然而,其在肺腺癌(ADC)中的具体作用尚未完全阐明。在这项研究中,通过实时定量 PCR 和 Western blot 检测了 PVT1、miR-378c 和溶质载体家族 2 成员 1(SLC2A1)的表达。双荧光素酶报告基因实验用于研究 PVT1 与 miR-378c 之间的关系,以及 miR-378c 与 SLC2A1 之间的关系。通过 MTT、划痕愈合和 Transwell 实验检测 PVT1 对肺 ADC 细胞增殖、侵袭和迁移的影响。结果显示,PVT1 在肺 ADC 细胞中高表达,过表达 PVT1 促进肺 ADC 细胞的增殖、迁移和侵袭。在肺 ADC 细胞中,PVT1 负调控 miR-378c 的表达,miR-378c 通过结合其 3'非翻译编码区负调控 SLC2A1 的表达。敲低 PVT1 抑制细胞增殖、迁移和侵袭能力,而 miR-378c 抑制剂或 SLC2A1 载体减弱了这种作用。沉默 PVT1 通过靶向 miR-378c 下调 SLC2A1 的表达,从而抑制肺 ADC 细胞的生长、迁移和侵袭。

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