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MicroRNA-27a-3p 通过靶向 NOV 替代剪接调节剂 1 促进胃癌中的上皮-间充质转化。

MicroRNA‑27a‑3p promotes epithelial‑mesenchymal transition by targeting NOVA alternative splicing regulator 1 in gastric cancer.

机构信息

Department of Gastrointestinal Surgery II, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.

Department of General Surgery, Cixi People's Hospital, Cixi, Zhejiang 315300, P.R. China.

出版信息

Mol Med Rep. 2020 Mar;21(3):1615-1622. doi: 10.3892/mmr.2020.10949. Epub 2020 Jan 17.

DOI:10.3892/mmr.2020.10949
PMID:32016460
Abstract

NOVA alternative splicing regulator 1 (NOVA1) dysregulation has been detected in the gastric cancer microenvironment. Decreased NOVA1 expression has been linked to the progression and poor prognosis of gastric cancer; however, the role of NOVA1 in regulating epithelial‑mesenchymal transition (EMT) remains unclear in this disease. Experimental evidence has shown that miR‑27a‑3p is a potential oncogene in gastric cancer. In the present study, we observed that miR‑27a‑3p expression was increased in gastric cancer and was inversely associated with overall survival. Overexpression of miR‑27a‑3p promoted EMT in AGS gastric cancer cells. Additionally, overexpression of miR‑27a‑3p inhibited NOVA1 expression, while silencing of NOVA1 promoted EMT in AGS cells. A total of 108 gastric cancer samples were examined for NOVA1 expression by immunohistochemistry. Decreased NOVA1 expression was linked to lymph node metastasis, tumor‑node‑metastasis stage and shorter overall survival. Therefore, these results indicated that NOVA1 could be a potential tumor suppressive gene and that miR‑27a‑3p promotes EMT by targeting NOVA1 in gastric cancer.

摘要

NOVA 剪接调控因子 1 (NOVA1) 在胃癌微环境中的失调已被检测到。NOVA1 表达降低与胃癌的进展和预后不良有关;然而,NOVA1 在调节上皮-间充质转化 (EMT) 中的作用在这种疾病中尚不清楚。实验证据表明,miR-27a-3p 是胃癌中的一种潜在癌基因。在本研究中,我们观察到 miR-27a-3p 在胃癌中的表达增加,与总生存期呈负相关。miR-27a-3p 的过表达促进了 AGS 胃癌细胞的 EMT。此外,miR-27a-3p 的过表达抑制了 NOVA1 的表达,而 NOVAl 的沉默则促进了 AGS 细胞的 EMT。对 108 例胃癌样本进行了免疫组织化学检测 NOVAl 表达。NOVA1 表达降低与淋巴结转移、肿瘤-淋巴结-转移分期和总生存期缩短有关。因此,这些结果表明 NOVA1 可能是一种潜在的肿瘤抑制基因,miR-27a-3p 通过靶向 NOVAl 在胃癌中促进 EMT。

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