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环状 RNA_100395 在肝癌增殖和转移中的作用。

Role of CircRNAs_100395 in Proliferation and Metastases of Liver Cancer.

机构信息

Department of General Surgery, Puning People's Hospital, Southern Medical University, Jieyang, Guangdong, China (mainland).

The First Clinical Medicine College, Southern Medical University, Guangzhou, Guangdong, China (mainland).

出版信息

Med Sci Monit. 2019 Aug 17;25:6181-6192. doi: 10.12659/MSM.915963.

DOI:10.12659/MSM.915963
PMID:31421050
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6709643/
Abstract

BACKGROUND Circular RNAs (circRNAs) are a kind of noncoding RNA with high cancer-specific expression, and great potential in regulating tumorigenesis. Among these, circRNA_100395 (circ_100395) has been reported to be downregulated in lung cancer, and participates in the process of tumor cell proliferation and metastasis. However, its expression and function in liver cancer remain unknown. MATERIAL AND METHODS Quantitative real-time polymerase chain reaction (RT-qPCR) was used to evaluate the expression level of circ_100395 and microRNAs-1228 (miR-1228) in liver cancer samples and the adjacent non-tumor tissues. Cell proliferation, apoptosis, invasion, migration, and epithelial-mesenchymal transition (EMT) pathway of circ_100395 upregulated cells were analyzed using a Cell Counting Kit-8 (CCK-8), flow cytometry, Transwell assay, and Western blot analysis. RESULTS We found that circ_100395 was downregulated in cancerous liver tissues relative to the adjacent normal tissues. The overexpression of circ_100395 was negatively associated with tumor differentiation, microvascular invasion, and portal vein tumor thrombosis. However, patients with higher circ_10039 expression tended to have better postoperative disease-free survival time. Moreover, upregulation of circ_100395 in liver cancer cells inhibited cell proliferation, induced apoptosis, then silenced the EMT pathway and reduced migration and invasion abilities, while this anti-tumor effect was significantly reversed by the downstream target, miR-1228. CONCLUSIONS circ_100395 appears to be a promising therapeutic target for liver cancer.

摘要

背景

环状 RNA(circRNAs)是一种具有高癌症特异性表达的非编码 RNA,在调节肿瘤发生方面具有巨大潜力。其中,circRNA_100395(circ_100395)已被报道在肺癌中下调,并参与肿瘤细胞增殖和转移的过程。然而,其在肝癌中的表达和功能尚不清楚。

材料和方法

实时定量聚合酶链反应(RT-qPCR)用于评估肝癌样本及其相邻非肿瘤组织中 circ_100395 和 microRNAs-1228(miR-1228)的表达水平。使用细胞计数试剂盒-8(CCK-8)、流式细胞术、Transwell 测定和 Western blot 分析来分析 circ_100395 上调细胞的增殖、凋亡、侵袭、迁移和上皮-间充质转化(EMT)途径。

结果

我们发现 circ_100395 在癌性肝组织中相对于相邻的正常组织下调。circ_100395 的过表达与肿瘤分化、微血管侵犯和门静脉癌栓呈负相关。然而,具有较高 circ_10039 表达的患者术后无病生存时间往往更长。此外,肝癌细胞中 circ_100395 的上调抑制细胞增殖,诱导细胞凋亡,从而沉默 EMT 途径并降低迁移和侵袭能力,而这种抗肿瘤作用可被下游靶标 miR-1228 显著逆转。

结论

circ_100395 似乎是肝癌有前途的治疗靶点。

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