环状RNA在肝细胞癌中的差异表达研究

Differentially expressed circular RNAs in human hepatocellular carcinoma

目的:探讨环状RNA(circ RNA)在肝细胞癌(HCC)与正常肝组织中表达谱的差异。方法:利用circ RNA芯片技术检测3例HCC组织和癌旁肝组织circ RNA的表达谱,经过对原始数据进行预处理、均一化后,找出差异表达的circ RNA(与癌旁肝组织比较,HCC组织中1.5倍以上变化并且差异有统计学意义的circ RNA定义为差异表达的circ RNA)。根据表达差异倍数较高和样本间一致性较好的原则筛选circ RNA,借助生物信息学软件预测可能受其调控的mi RNA,结合文献检索初步确定可能在HCC中具有重要作用的circ RNA。结果:与癌旁肝组织比较,HCC组织中的circ RNA表达谱发生了明显变化。HCC组织中,1.5倍以上变化的circ RNA共82条,其中上调21条,下调61条;5倍以上变化的circ RNA共3条,其中上调2条,下调1条。最终筛选出在HCC组织中明显上调的hsa-circ-0043278(8.15倍,P=0.002)、hsacirc-0006220(12.73倍,P=0.033)和明显下调的hsa-circ-0065214(6.28倍,P=0.019);生物信息学分析和文献检索显示,hsa-mi R-520可能受hsa-circ-0043278和hsa-circ-0006220调控而影响HCC的发生和进展。结论:HCC组织circ RNA表达谱发生了显著变化;hsa-circ-0043278和hsa-circ-0006220可能在HCC的发生和进展中发挥重要作用。

Objective： To analyze the difference in circular RNA （circRNA） expression profiles between hepatocellular carcinoma （HCC） tissue and normal liver tissue. Methods： q-he circRNA expression profiles in 3 paired specimens of HCC tissue and its adjacent liver tissue were detected by using the human circRNA microarray. After preprocessing and homogenization of the original data, the differentially expressed circRNAs were searched out （the circRNA in HCC tissue showed a greater than 1.5-fold change which was also statistically significant compared with adjacent liver tissue and was regarded as differentially expressed circRNA）. Then, after these circRNAs screening according to the principle of higher fold change and better consistency and their putatively targeting miRNAs prediction by bioinformatics software combined with literature review, the circRNAs that potentially contribute to HCC development were preliminarily identified. Results： The circRNA expression profile in HCC showed remarkable changes compared with adjacent hepatic tissue. In HCC tissue, a total of 82 circRNAs showed a greater than 1.5-fold change, and of them, 21 were up- regulated and 61 were down-regulated; a total of 3 circRNAs showed a greater than 5-fold change, and of them, 2 were up-regulated and 1 was down-regulated. The significantly up-regulated circRNA hsa-circ-0043278 （8.15 fold, P-0.002） and hsa-circ-0006220 （12.73 fold, P=0.033）, and significantly down-regulated circRNA hsacirc-0065214 （6.28 fold, P=0.019） were finally obtained after screening. Bioinformatics analysis and literature review suggested that hsa-miR-520 was potentially regulated contributed to the occurrence and development of HCC by hsa-circ-0043278 and hsa-circ-0006220, which Conclusion： The circRNA expression profile in HCC is greatly changed. Hsa-circ-0043278 and hsa-circ-0006220 may play important roles in the occurrence and development of HCC.