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miR-874 通过靶向 SPAG9 抑制胃癌细胞增殖。

miR-874 inhibits gastric cancer cell proliferation by targeting SPAG9.

机构信息

Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, China.

Department of Respiration Medicine, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, China.

出版信息

BMC Cancer. 2020 Jun 5;20(1):522. doi: 10.1186/s12885-020-06994-z.

Abstract

BACKGROUND

microRNAs (miRNAs) play essential roles in the development and progression of gastric cancer (GC). Although aberrant miR-874 expression has been reported in various human cancers, its role in GC remains obscure.

METHODS

miR-874 expression was assessed by real-time quantitative polymerase chain reaction (RT-qPCR) in 62 matched GC and adjacent normal tissues, as well as in GC cell lines and immortalized human gastric epithelial cells. CCK8 assay, colony formation assay, and flow cytometry were used to assess the role of miR-874 in GC cell proliferation and apoptosis in vitro. Additionally, to determine the effects of miR-874 on GC cell proliferation and apoptosis in vivo, BALB/c nude mice were injected with GC cells transfected with a miR-874 mimic. The role of miR-874 in SPAG9 expression was assessed by luciferase assay, Western blotting, and RT-qPCR.

RESULTS

miR-874 was downregulated in GC cell lines and tissues. miR-874 overexpression in GC cells led to inhibition of cell proliferation and induction of apoptosis. Moreover, SPAG9 was identified as a direct miR-874 target, the expression of which was suppressed by miR-874. SPAG9 overexpression markedly promoted GC cell proliferation.

CONCLUSIONS

miR-874 inhibited cell proliferation and induced apoptosis in GC cells. SPAG9 downregulation was crucial for the tumor-suppressive effects of miR-874. Hence, the miR-874/SPAG9 axis could serve as a novel therapeutic target in GC.

摘要

背景

微小 RNA(miRNA)在胃癌(GC)的发生和发展中起着至关重要的作用。尽管已经在各种人类癌症中报道了异常的 miR-874 表达,但它在 GC 中的作用仍不清楚。

方法

通过实时定量聚合酶链反应(RT-qPCR)在 62 对 GC 和相邻正常组织以及 GC 细胞系和永生化人胃上皮细胞中评估 miR-874 的表达。CCK8 测定、集落形成测定和流式细胞术用于评估 miR-874 对 GC 细胞体外增殖和凋亡的作用。此外,为了确定 miR-874 对 GC 细胞体内增殖和凋亡的影响,将转染 miR-874 模拟物的 GC 细胞注射到 BALB/c 裸鼠中。通过荧光素酶测定、Western blot 和 RT-qPCR 评估 miR-874 对 SPAG9 表达的作用。

结果

miR-874 在 GC 细胞系和组织中下调。GC 细胞中 miR-874 的过表达导致细胞增殖抑制和凋亡诱导。此外,SPAG9 被鉴定为 miR-874 的直接靶标,其表达受 miR-874 抑制。SPAG9 的过表达显着促进 GC 细胞增殖。

结论

miR-874 抑制 GC 细胞的增殖并诱导其凋亡。SPAG9 下调对 miR-874 的肿瘤抑制作用至关重要。因此,miR-874/SPAG9 轴可作为 GC 的新型治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ffa/7275545/6f6e97abd607/12885_2020_6994_Fig1_HTML.jpg

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