hsa-miR-875-5p 通过靶向 USF2 抑制胃癌的肿瘤发生和 TGF-β 信号通路。
hsa-miR-875-5p inhibits tumorigenesis and suppresses TGF-β signalling by targeting USF2 in gastric cancer.
机构信息
Department of Gastroenterological Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, China.
Department of Gastroenterological Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China.
出版信息
J Transl Med. 2022 Mar 7;20(1):115. doi: 10.1186/s12967-022-03253-6.
BACKGROUND
Gastric cancer (GC) is one of the most common malignancies, and an increasing number of studies have shown that its pathogenesis is regulated by various miRNAs. In this study, we investigated the role of miR-875-5p in GC.
METHODS
The expression of miR-875-5p was detected in human GC specimens and cell lines by miRNA qRT-PCR. The effect of miR-875-5p on GC proliferation was determined by Cell Counting Kit-8 (CCK-8) proliferation and 5-ethynyl-2'-deoxyuridine (EdU) assays. Migration and invasion were examined by transwell migration and invasion assays as well as wound healing assays. The interaction between miR-875-5p and its target gene upstream stimulatory factor 2(USF2) was verified by dual luciferase reporter assays. The effects of miR-875-5p in vivo were studied in xenograft nude mouse models. Related proteins were detected by western blot.
RESULTS
The results showed that miR-875-5p inhibited the proliferation, migration and invasion of GC cells in vitro and inhibited tumorigenesis in vivo. USF2 was proved to be a direct target of miR-875-5p. Knockdown of USF2 partially counteracted the effects of miR-875-5p inhibitor. Overexpression of miR-875-5p could inhibit proliferation, migration and invasion and suppress the TGF-β signalling pathway by downregulating USF2.
CONCLUSIONS
MiR-875-5p can inhibit the progression of GC by directly targeting USF2. And in the future, miR-875-5p is expected to be a potential target for GC diagnosis and treatment.
背景
胃癌（GC）是最常见的恶性肿瘤之一，越来越多的研究表明其发病机制受多种 miRNAs 调控。本研究旨在探讨 miR-875-5p 在 GC 中的作用。
方法
通过 miRNA qRT-PCR 检测人 GC 标本和细胞系中 miR-875-5p 的表达。通过 Cell Counting Kit-8（CCK-8）增殖和 5-乙炔基-2'-脱氧尿苷（EdU）检测评估 miR-875-5p 对 GC 增殖的影响。通过 Transwell 迁移和侵袭实验以及划痕愈合实验检测迁移和侵袭能力。通过双荧光素酶报告实验验证 miR-875-5p 与其靶基因上游刺激因子 2（USF2）之间的相互作用。在异种移植裸鼠模型中研究 miR-875-5p 的体内作用。通过 Western blot 检测相关蛋白。
结果
结果表明，miR-875-5p 抑制 GC 细胞的体外增殖、迁移和侵袭，并抑制体内肿瘤生成。USF2 被证实是 miR-875-5p 的直接靶基因。USF2 敲低部分逆转了 miR-875-5p 抑制剂的作用。miR-875-5p 的过表达通过下调 USF2 抑制增殖、迁移和侵袭，并抑制 TGF-β 信号通路。
结论
miR-875-5p 可通过直接靶向 USF2 抑制 GC 的进展。未来，miR-875-5p 有望成为 GC 诊断和治疗的潜在靶点。
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