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环状 RNA 与信使 RNA 共表达网络分析表明,环状 RNA hsa_circ_0047905、hsa_circ_0138960 和 has-circRNA7690-15 是胃癌的候选癌基因。

Analysis of co-expression networks for circular RNAs and mRNAs reveals that circular RNAs hsa_circ_0047905, hsa_circ_0138960 and has-circRNA7690-15 are candidate oncogenes in gastric cancer.

机构信息

a Department of Gastroenterological Surgery , Laboratory of Surgical Oncology , Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research , Peking University People's Hospital , No.11 Xizhimen South Street, Xicheng District, Beijing , People's Republic of China.

b Department of Breast Center , Peking University People's Hospital , No.11 Xizhimen South Street, Xicheng District, Beijing , People's Republic of China.

出版信息

Cell Cycle. 2017;16(23):2301-2311. doi: 10.1080/15384101.2017.1380135. Epub 2017 Nov 9.

Abstract

Accumulating evidence has suggested that circular RNAs (circRNAs) play important roles in oncogenesis and tumor progression. However, our knowledge of circRNAs in gastric cancer (GC) remains limited. To investigate circRNAs involved in GC oncogenesis, we examined differentially-expressed circRNAs and mRNAs in GC tissues and paired noncancerous mucosa tissues using circRNA and mRNA microarrays. Next, we built gene co-expression networks according to the degree of correlation to predict the critical circRNAs in GC. Through bioinformatics analysis, we observed three newly identified circRNAs that are substantially upregulated in GC: hsa_circ_0047905, hsa_circ_0138960 and has-circRNA7690-15. Additionally, hsa_circ_0047905 and hsa_circ_0138960 positively correlated with their parental gene mRNA. Knockdown of hsa_circ_0047905, hsa_circ_0138960 and has-circRNA7690-15 in GC cells, resulted in downregulation of parental gene expression. Functional assays suggested that inhibition of these three circular RNAs suppresses GC cell proliferation and invasion in vitro. Those findings suggest that hsa_circ_0047905, hsa_circ_0138960 and has-circRNA7690-15 might act as tumor promoters in the pathogenesis of gastric cancer.

摘要

越来越多的证据表明,环状 RNA(circRNA)在肿瘤发生和肿瘤进展中发挥重要作用。然而,我们对胃癌(GC)中 circRNA 的了解仍然有限。为了研究参与 GC 致癌作用的 circRNAs,我们使用 circRNA 和 mRNA 微阵列检测了 GC 组织和配对非癌性粘膜组织中差异表达的 circRNAs 和 mRNAs。接下来,我们根据相关性程度构建基因共表达网络,以预测 GC 中的关键 circRNA。通过生物信息学分析,我们观察到三种在 GC 中明显上调的新鉴定的 circRNA:hsa_circ_0047905、hsa_circ_0138960 和 has-circRNA7690-15。此外,hsa_circ_0047905 和 hsa_circ_0138960 与它们的亲本基因 mRNA 呈正相关。GC 细胞中 hsa_circ_0047905、hsa_circ_0138960 和 has-circRNA7690-15 的敲低导致亲本基因表达下调。功能测定表明,抑制这三种环状 RNA 可抑制 GC 细胞在体外的增殖和侵袭。这些发现表明 hsa_circ_0047905、hsa_circ_0138960 和 has-circRNA7690-15 可能在胃癌的发病机制中作为肿瘤促进物发挥作用。

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