hsa-miR-875-5p inhibits tumorigenesis and suppresses TGF-β signalling by targeting USF2 in gastric cancer.
hsa-miR-875-5p inhibits tumorigenesis and suppresses TGF-β signalling by targeting USF2 in gastric cancer.
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DOI：
10.1186/s12967-022-03253-6
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发表时间：
2022-03-07
影响因子：
7.4
通讯作者：
Guo X
中科院分区：
文献类型：
--
作者：
Gao S;Zhang Z;Wang X;Ma Y;Li C;Liu H;Jing C;Li L;Guo X
胃癌（Gastric cancer， 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mirna的调控。在这项研究中，我们研究了miR-875-5p在GC中的作用。通过miRNA qRT-PCR检测miR-875-5p在人GC标本和细胞系中的表达。通过细胞计数试剂盒-8 （CCK-8）增殖和5-乙基-2′-脱氧尿苷（EdU）测定测定miR-875-5p对GC增殖的影响。通过跨井迁移和侵袭试验以及伤口愈合试验检测迁移和侵袭。通过双荧光素酶报告基因测定证实了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在体内的作用。western blot检测相关蛋白。结果表明，miR-875-5p在体外抑制胃癌细胞的增殖、迁移和侵袭，在体内抑制肿瘤发生。USF2被证明是miR-875-5p的直接靶点。USF2的敲低部分抵消了miR-875-5p抑制剂的作用。过表达miR-875-5p可通过下调USF2抑制增殖、迁移和侵袭，抑制TGF-β信号通路。MiR-875-5p可通过直接靶向USF2抑制GC的进展。在未来，miR-875-5p有望成为胃癌诊断和治疗的潜在靶点。
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. 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. 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. 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.
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DOI：
10.1146/annurev.pathol.4.110807.092222
发表时间：
2009
期刊：
Annual review of pathology
影响因子：
--
作者：
Lee YS;Dutta A
通讯作者：
Dutta A
影响因子：
2.4
作者：
Bhaskaran M;Mohan M
通讯作者：
Mohan M
影响因子：
14.9
作者：
SIRITO, M;LIN, Q;SAWADOGO, M
通讯作者：
SAWADOGO, M
影响因子：
64.5
作者：
CARTHEW, RW;CHODOSH, LA;SHARP, PA
通讯作者：
SHARP, PA
影响因子：
2.7
作者：
Kang N;Ou Y;Wang G;Chen J;Li D;Zhan Q
通讯作者：
Zhan Q