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胃肿瘤发生过程中的 microRNA 表达谱。

MicroRNA Expression Profiles in Gastric Carcinogenesis.

机构信息

Department of Biomedical Science, Seoul National University Graduate School, Seoul, Korea.

Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

出版信息

Sci Rep. 2018 Sep 26;8(1):14393. doi: 10.1038/s41598-018-32782-8.

Abstract

Intestinal-type gastric carcinoma exhibits a multistep carcinogenic sequence from adenoma to carcinoma with a gradual increase in genomic alterations. But the roles of microRNAs (miRNA) in this multistage cascade are not fully explored. To identify differentially expressed miRNA (DEM) during early gastric carcinogenesis, we performed miRNA microarray profiling with 24 gastric cancers and precursor lesions (7 early gastric cancer [EGC], 3 adenomas with high-grade dysplasia, 4 adenomas with low-grade dysplasia, and 10 adjacent normal tissues). Alterations in the expression of 132 miRNA were detected; these were categorized into three groups based on their expression patterns. Of these, 42 miRNAs were aberrantly expressed in EGC. Five miRNA (miR-26a, miR-375, miR-574-3p, miR-145, and miR-15b) showed decreased expression since adenoma. Expression of two miRNA, miR-200C and miR-29a, was down-regulated in EGCs compared to normal mucosa or adenomas. Six miRNA (miR-601, miR-107, miR-18a, miR-370, miR-300, and miR-96) showed increased expression in gastric cancer compared to normal or adenoma samples. Five representative miRNAs were further validated with RT-qPCR in independent 77 samples. Taken together, these results suggest that the dysregulated miRNA show alterations at the early stages of gastric tumorigenesis and may be used as a candidate biomarker.

摘要

肠型胃癌表现为从腺瘤到癌的多步骤致癌序列,基因组改变逐渐增加。但是,miRNA(miRNA)在这一多阶段级联反应中的作用尚未完全探索。为了鉴定早期胃癌发生过程中差异表达的miRNA(DEM),我们使用 24 例胃癌和前体病变(7 例早期胃癌[EGC]、3 例高级别异型增生腺瘤、4 例低级别异型增生腺瘤和 10 例相邻正常组织)进行 miRNA 微阵列分析。检测到 132 个 miRNA 的表达发生改变;根据其表达模式将其分为三组。其中,42 个 miRNA 在 EGC 中表达异常。有 5 个 miRNA(miR-26a、miR-375、miR-574-3p、miR-145 和 miR-15b)从腺瘤开始表达减少。与正常黏膜或腺瘤相比,miR-200C 和 miR-29a 的表达在 EGC 中下调。与正常或腺瘤样本相比,有 6 个 miRNA(miR-601、miR-107、miR-18a、miR-370、miR-300 和 miR-96)在胃癌中表达增加。进一步用 RT-qPCR 在 77 个独立样本中验证了 5 个代表性 miRNA。总之,这些结果表明失调的 miRNA 在胃癌发生的早期阶段发生改变,可能作为候选生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/100e/6158169/792fe4b6e13a/41598_2018_32782_Fig1_HTML.jpg

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