miR-874-3p 通过海绵吸附长链非编码 RNA 00922（LINC00922）并靶向甘油磷酸二酯磷酸二酯酶结构域包含 5（GDPD5）抑制胃癌细胞的迁移和侵袭，促进凋亡和顺铂敏感性。
MiR-874-3p represses the migration and invasion yet promotes the apoptosis and cisplatin sensitivity via being sponged by long intergenic non-coding RNA 00922 (LINC00922) and targeting Glycerophosphodiester Phosphodiesterase Domain Containing 5 (GDPD5) in gastric cancer cells.
机构信息
Division of Gastrointestinal Surgery, Department of General Surgery, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huaian, Jiangsu, China.
Department of General Surgery, Lianshui People's Hospital Affiliated to Kangda College of Nanjing Medical University, Huaian, Jiangsu, China.
出版信息
Bioengineered. 2022 Mar;13(3):7082-7104. doi: 10.1080/21655979.2022.2045831.
Our study mainly reports the specific mechanisms of microRNA (miR)-874-3p on drug resistance in gastric cancer (GC). Clinical specimen was collected. The upstream long non-coding RNA (lncRNA) and the downstream gene of miR-874-3p were predicted using bioinformatic analysis with the results being ascertained with dual-luciferase reporter assay. The viability, apoptosis, migration and invasion of transfected GC cells with or without cisplatin (DDP) treatment were evaluated by Cell Counting Kit-8 (CCK-8), flow cytometric, Scratch, and Transwell assays. An animal xenograft model was constructed. Expressions of long intergenic non-coding RNA 00922 (LINC00922), miR-874-3p and potential target genes were quantified by quantitative real-time polymerase-chain reaction (qRT-PCR) and Western blot. MiR-874-3p, which was lower-expressed in drug-resistant GC tissues and cells, was upregulated to repress the viability, migration and invasion but enhance the apoptosis and sensitivity in GC cells with or without DDP resistance. Downregulation of miR-874-3p eliminated the effects of silenced LINC00922, a upstream lncRNA of miR-874-3p, on cell viability, apoptosis, migration and invasion, as well as the expressions of Glycerophosphodiester Phosphodiesterase Domain Containing 5 (GDPD5) and the downstream gene of miR-874-3p in DDP-resistant GC cells. GDPD5 silencing diminished the effects of miR-874-3p downregulation on GDPD5 expression, viability, migration and invasion of DDP-resistant GC cells. Additionally, LINC00922 silencing enhanced the inhibitory effect of DDP on tumor growth, whereas reversing the effects of DDP on LINC00922, miR-874-3p and GDPD5 expressions in tumors. MiR-874-3p, an miRNA, which is sponged by LINC00922 and targets GDPD5, inhibits the GC progression yet enhances the DDP sensitivity in GC.
本研究主要报道了 microRNA（miR）-874-3p 对胃癌（GC）耐药的具体机制。收集临床标本，通过生物信息学分析预测 miR-874-3p 的上游长链非编码 RNA（lncRNA）和下游基因，并通过双荧光素酶报告基因实验进行验证。用细胞计数试剂盒-8（CCK-8）、流式细胞术、划痕和 Transwell 检测转染顺铂（DDP）处理或未处理 GC 细胞的活力、凋亡、迁移和侵袭。构建动物异种移植模型。通过定量实时聚合酶链反应（qRT-PCR）和 Western blot 定量检测长基因间非编码 RNA 00922（LINC00922）、miR-874-3p 和潜在靶基因的表达。miR-874-3p 在耐药 GC 组织和细胞中表达较低，上调 miR-874-3p 可抑制 GC 细胞的活力、迁移和侵袭，增强其对 DDP 耐药的凋亡和敏感性。下调 miR-874-3p 消除了 miR-874-3p 的上游 lncRNA LINC00922 沉默对细胞活力、凋亡、迁移和侵袭以及 DDP 耐药 GC 细胞中 miR-874-3p 下游基因 Glycerophosphodiester Phosphodiesterase Domain Containing 5（GDPD5）表达的影响。沉默 GDPD5 可减弱 miR-874-3p 下调对 DDP 耐药 GC 细胞 GDPD5 表达、活力、迁移和侵袭的影响。此外，沉默 LINC00922 增强了 DDP 对肿瘤生长的抑制作用，而逆转了 DDP 对肿瘤中 LINC00922、miR-874-3p 和 GDPD5 表达的影响。miR-874-3p 是一种 miRNA，被 LINC00922 海绵吸收并靶向 GDPD5，抑制 GC 进展，增强 GC 对 DDP 的敏感性。
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