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长链非编码RNA-RMRP通过充当miR-206的海绵促进癌变,并被用作胃癌的一种新型生物标志物。

LncRNA-RMRP promotes carcinogenesis by acting as a miR-206 sponge and is used as a novel biomarker for gastric cancer.

作者信息

Shao Yongfu, Ye Meng, Li Qier, Sun Weiliang, Ye Guoliang, Zhang Xinjun, Yang Yunben, Xiao Bingxiu, Guo Junming

机构信息

Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, 315211, China.

Current address: Department of Gastroenterology, The Affiliated Hospital of Ningbo University School of Medicine, Ningbo, 315020, China.

出版信息

Oncotarget. 2016 Jun 21;7(25):37812-37824. doi: 10.18632/oncotarget.9336.

Abstract

Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis. However, the mechanisms of most lncRNAs in cancers are largely unknown. Because the RNA component of mitochondrial RNA processing endoribonuclease (RMRP) is one of the dysregulated lncRNAs in gastric cancer, this study explored its molecular mechanisms in carcinogenesis. RMRP levels in 792 tissues, plasma and gastric juices from patients with various stages of gastric tumorigenesis were analyzed by quantitative reverse transcription-polymerase chain reaction. Overexpression and RNA interference were used to manipulate RMRP expression by RMRP expression vector and small interfering RNAs, respectively. Its mechanisms were evaluated by flow cytometry, real-time cell analysis, plate colony formation assays, and xenograft models. RMRP levels in tissue, plasma and gastric juices from patients with gastric cancer were significantly different from those from controls. Its levels were significantly associated with Borrmann type and metastasis. Plasma and gastric juice RMRP had higher sensitivity and specificity than commonly used markers (such as carcinoembryonic antigen and carbohydrate antigen 19-9). Knockdown of RMRP significantly inhibited cell proliferation in vitro and in vivo, whereas overexpression of RMRP promoted cell growth. Acting as a miR-206 sponge, RMRP modulated cell cycle by regulating Cyclin D2 expression. RMRP plays a crucial role in gastric cancer occurrence and can be used as a novel biomarker for gastric cancer.

摘要

长链非编码RNA(lncRNAs)在肿瘤发生过程中发挥着关键作用。然而,大多数lncRNAs在癌症中的作用机制仍 largely未知。由于线粒体RNA加工内切核糖核酸酶(RMRP)的RNA成分是胃癌中失调的lncRNAs之一,本研究探讨了其在致癌作用中的分子机制。通过定量逆转录-聚合酶链反应分析了792例不同胃癌发生阶段患者的组织、血浆和胃液中的RMRP水平。分别使用RMRP表达载体和小干扰RNA通过过表达和RNA干扰来操纵RMRP表达。通过流式细胞术、实时细胞分析、平板集落形成试验和异种移植模型评估其机制。胃癌患者组织、血浆和胃液中的RMRP水平与对照组显著不同。其水平与Borrmann分型和转移显著相关。血浆和胃液RMRP比常用标志物(如癌胚抗原和糖类抗原19-9)具有更高的敏感性和特异性。敲低RMRP显著抑制体外和体内细胞增殖,而RMRP过表达促进细胞生长。作为miR-206的海绵,RMRP通过调节细胞周期蛋白D2表达来调节细胞周期。RMRP在胃癌发生中起关键作用,可作为胃癌的新型生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a1e/5122351/216b50f6a329/oncotarget-07-37812-g001.jpg

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