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hnRNPA1 的高表达通过诱导 EMT 促进胃癌细胞侵袭。

High expression of hnRNPA1 promotes cell invasion by inducing EMT in gastric cancer.

机构信息

Department of Gastroenterology, Longgang People's Hospital, Shenzhen, Guangdong 518172, P.R. China.

Department of Pathology, The First People's Hospital of Xinxiang City, Xinxiang, Henan 453100, P.R. China.

出版信息

Oncol Rep. 2018 Apr;39(4):1693-1701. doi: 10.3892/or.2018.6273. Epub 2018 Feb 16.


DOI:10.3892/or.2018.6273
PMID:29484423
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5868405/
Abstract

Advanced gastric cancer (GC) has a poor prognosis and its treatment strategies are not very efficient. Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) has emerged as a plausible GC marker, however the role and molecular mechanism of hnRNPA1 in cell invasion and migration remains unknown. In the present study, the gene expression across normal and tumor tissue (GENT) database was used to evaluate the mRNA expression of hnRNPA1 in various types of cancer. Western blot analysis (WB) and immunohistochemistry (IHC) were performed to detect the protein expression of hnRNPA1 in GC tissues and adjacent non‑tumor tissues. The expression of multiple oncogenes was detected by western blot analysis and quantitative RT‑PCR in hnRNPA1 overexpressing GC cells. Soft agar colony formation, EdU incorporation, wound healing and invasion assays were applied to verify the role of hnRNPA1 in anchorage‑independent cell growth, migration and invasion in GC cells. Epithelial‑to‑mesenchymal transition (EMT) markers were detected by immunofluorescence, western blot analysis and IHC in vitro. A nude mice model of metastasis carcinoma was established to confirm the role of hnRNPA1 during EMT in vivo. Our results revealed that hnRNPA1 was significantly upregulated in GC tissue. HnRNPA1 overexpression significantly induced cell growth, migration and invasion ability in GC cells. In addition, hnRNPA1 promoted EMT of GC cells in vitro and in vivo. These findings indicated that hnRNPA1 is highly expressed in GC and promoted invasion by inducing EMT transition in GC cells. Thus, hnRNPA1 may be a potential therapeutic target for GC.

摘要

晚期胃癌(GC)预后较差,其治疗策略效果不佳。异质性核核糖核蛋白 A1(hnRNPA1)已成为一种合理的 GC 标志物,但其在细胞侵袭和迁移中的作用和分子机制尚不清楚。本研究利用基因表达贯穿正常组织和肿瘤组织(GENT)数据库评估 hnRNPA1 在各种癌症中的 mRNA 表达。通过 Western blot 分析(WB)和免疫组织化学(IHC)检测 hnRNPA1 在 GC 组织和相邻非肿瘤组织中的蛋白表达。通过 Western blot 分析和定量 RT-PCR 检测 hnRNPA1 过表达 GC 细胞中多种癌基因的表达。通过软琼脂集落形成、EdU 掺入、划痕愈合和侵袭实验验证 hnRNPA1 在 GC 细胞锚定非依赖性细胞生长、迁移和侵袭中的作用。通过免疫荧光、Western blot 分析和 IHC 在体外检测上皮-间充质转化(EMT)标志物。建立转移癌裸鼠模型,体内验证 hnRNPA1 在 EMT 中的作用。研究结果表明 hnRNPA1 在 GC 组织中明显上调。hnRNPA1 过表达显著诱导 GC 细胞的生长、迁移和侵袭能力。此外,hnRNPA1 在体外和体内促进了 GC 细胞的 EMT。这些发现表明 hnRNPA1 在 GC 中高表达,并通过诱导 GC 细胞 EMT 过渡促进侵袭。因此,hnRNPA1 可能是 GC 的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/851f/5868405/9767b5915d79/OR-39-04-1693-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/851f/5868405/2e2146155f95/OR-39-04-1693-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/851f/5868405/c3b848f74811/OR-39-04-1693-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/851f/5868405/45ca6ea13aad/OR-39-04-1693-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/851f/5868405/9767b5915d79/OR-39-04-1693-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/851f/5868405/2e2146155f95/OR-39-04-1693-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/851f/5868405/c3b848f74811/OR-39-04-1693-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/851f/5868405/45ca6ea13aad/OR-39-04-1693-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/851f/5868405/9767b5915d79/OR-39-04-1693-g03.jpg

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