Circular RNA hsa_circ_0002124 promotes hepatocellular carcinoma cell proliferation through the MAPK pathway.
Circular RNA hsa_circ_0002124 promotes hepatocellular carcinoma cell proliferation through the MAPK pathway.
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圆形RNA HSA_CIRC_0002124通过MAPK途径促进肝细胞癌细胞增殖。
DOI：
10.21037/tcr.2019.01.38
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发表时间：
2019-04
影响因子：
0.9
通讯作者：
Liu X
中科院分区：
文献类型：
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作者：
Fang Z;Fan R;Lu Y;Sun Y;Zhao C;Liu L;Liu X
2013年首次报道的Hsa_circ_0002124来源于NuSAP 1。然而，其在肝细胞癌（HCC）中的作用及其调控机制仍有待研究。首先，通过特异性会聚和发散引物扩增对hsa_circ_0002124进行结构验证。使用qPCR测定肝癌组织和多种HCC细胞系中的hsa_circ_0002124表达。此外，使用97 H细胞中的敲低和过表达hsa_circ_0002124来检查HCC细胞中hsa_circ_0002124的细胞功能。MTS法检测细胞增殖情况，Transwell法检测细胞增殖和侵袭能力，流式细胞仪检测细胞周期和凋亡情况。此外，进行GO和KEGG分析以揭示HCC中的关键功能和通路。使用Cytoscape软件构建hsa_circ_0002124与其下游miRNAs和基因之间的相互作用网络。Western blotting检测hsa_circ_0002124基因敲低和过表达对97 H细胞MAPK通路关键蛋白（p-JNK、JNK、p-ERK、ERK、p-P38、P38和c-Myc）表达的影响。Hsa_circ_0002124在肝癌细胞和肝癌组织中高表达。此外，hsa_circ_0002124在97 H细胞中的敲低导致细胞增殖、细胞侵袭和迁移的抑制，同时促进细胞凋亡和细胞周期转化。在97 H细胞中过表达的hsa_circ_0002124中可以检测到细胞功能的相反情况。KEGG和相互作用网络分析表明hsa_circ_0002124可能是miRNAs的分子海绵，调控MAPK通路中关键蛋白的表达。敲低hsa_circ_0002124处理的97 H细胞中的p-JNK/JNK、p-ERK/ERK、p-P38/P38和c-Myc表达显著低于正常97 H细胞，而过表达hsa_circ_0002124处理的97 H细胞中的这些表达显著高于模拟载体处理的97 H细胞。Hsa_circ_0002124可能成为HCC早期诊断和治疗的潜在生物标志物。
Hsa_circ_0002124, which was first reported in 2013, is derived from NuSAP1. However, its role in hepatocellular carcinoma (HCC) and its regulatory mechanisms remain to be investigated. First, hsa_circ_0002124 was structurally validated via specific convergent and divergent primer amplification. The hsa_circ_0002124 expression in the liver cancer tissues and multiple HCC cell lines were determined using qPCR. Further, the cell functions of hsa_circ_0002124 in HCC cells were examined using knockdown and overexpressed hsa_circ_0002124 in 97H cells. The cell proliferation was assessed using MTS assay, cell proliferation and invasion capacities were evaluated using Transwell culture system, and cell cycle progression and apoptosis were analyzed using flow cytometry. Further, GO and KEGG analyses were performed to uncover the key function and pathways in HCC. The interaction networks between hsa_circ_0002124 and its downstream miRNAs and genes were constructed using Cytoscape software. The key protein expressions (p-JNK, JNK, p-ERK, ERK, p-P38, P38, and c-Myc) of the MAPK pathway in 97H cells with knockdown and overexpressed hsa_circ_0002124 treatments were detected using Western blotting. Hsa_circ_0002124 was highly expressed in the HCC cells and liver cancer tissues. Moreover, the knockdown hsa_circ_0002124 in 97H cells resulted in the repression of cell proliferation, cell invasion, and migration, with simultaneous promotion of cell apoptosis and cell cycle transformation. The opposing situations of cell function could be detected in overexpressed hsa_circ_0002124 in 97H cells. KEGG and interaction network analysis of hsa_circ_0002124 indicated that hsa_circ_0002124 could be a molecular sponge of miRNAs, which regulates the key protein expressions in the MAPK pathway. The p-JNK/JNK, p-ERK/ERK, p-P38/P38, and c-Myc expressions in knockdown hsa_circ_0002124-treated 97H cells were significantly lower than in normal 97H cells, whereas these expressions in overexpressed hsa_circ_0002124-treated 97H cells were significantly higher than in mock vector-treated 97H cells. Hsa_circ_0002124 could be a potential biomarker for the early diagnosis and treatment of HCC.