多发性骨髓瘤环状RNA的差异表达情况及生物学功能研究  

Differential expression and biological function of circRNAs in multiple myeloma

作　　者：王艳芳[1] 张朕豪 王化[1] 郤连永 董菲[1] 景红梅[1] WANG Yanfang;ZHANG Zhenhao;WANG Hua;XI Lianyong;DONG Fei;JING Hongmei(Department of Hematology,Peking University Third Hospital,Beijing 100191,China)

机构地区：[1]北京大学第三医院血液科,北京100191

出　　处：《实用肿瘤学杂志》2023年第4期313-319,共7页Practical Oncology Journal

基　　金：国家自然科学基金(编号:81700192)。

摘　　要：目的研究多发性骨髓瘤(MM)中环状RNA(circRNAs)的差异表达情况,并对其生物学功能进行预测。方法收集2023年1月—2月在北京大学第三医院血液科就诊的5例MM患者和同期3例健康志愿者的骨髓样本进行转录组测序,确定MM中差异表达的circRNAs;对circRNAs的miRNA结合位点进行预测;对差异circRNAs进行GO和KEGG富集分析;利用实时荧光定量PCR(qRT-PCR)对部分circRNAs进行验证。结果在MM和正常对照骨髓样本中发现926个差异表达circRNAs,其中上调的818个,下调的108个。这些差异circRNAs具有大量的miRNA结合位点,如miR-619-5p、miR-17-5p、miR-20a-5p等。GO分析显示这些差异circRNAs主要参与细胞的蛋白质代谢、有机物代谢、含氮化合物代谢等生物代谢过程。KEGG分析显示Rap1、FoxO、AMPK等信号通路明显富集。通过qRT-PCR实验对表达显著上调的4个circRNAs进行验证,发现circ_0004524和circ_0003823明显上调,与测序结果一致。结论MM患者具有独特的circRNAs表达谱,对其进行深入的功能和机制研究有助于为MM的诊断和治疗提供潜在的分子标志物。Objective The objective of this study was to explore the differential expression of circular RNAs(circRNAs)in multiple myeloma(MM)and predict their biological function.Methods Bone marrow samples of five MM patients who visited the department of hematology,Peking University Third Hospital from January to February 2023 and three healthy volunteers during the same period were collected for transcriptome sequencing to determine the differentially expressed circRNAs in MM.The miRNAs binding sites of circRNAs were predicted.GO and KEGG enrichment analyses were performed on differential circRNAs.The real-time fluorescence quantitative PCR(qRT-PCR)was used to verify some circRNAs.Results A total of 926 differentially expressed circRNAs were found in MM and normal control bone marrow samples,of which 818 were up-regulated and 108 were down-regulated.These differentially circRNAs had a large number of miRNA binding sites,such as miR-619-5p,miR-17-5p,miR-20a-5p,et al.GO analysis showed that these differential circRNAs were mainly involved in biological metabolism processes such as cell protein metabolism,organic matter metabolism,and nitrogen-containing compound metabolism.KEGG analysis showed that signal pathways such as Rap1,FoxO,and AMPK were significantly enriched.The 4 circRNAs whose expression was significantly up-regulated were verified through qRT-PCR experiments,and it was found that circ_0004524 and circ_0003823 were significantly up-regulated,consistent with sequencing results.Conclusion MM patients have unique circRNAs expression profiles,and studies in-depth functional and mechanism will help provide potential molecular markers for the diagnosis and treatment of MM.

关 键 词：多发性骨髓瘤 环状RNA 生物信息学分析 信号通路 

分 类 号：R733.3[医药卫生—肿瘤]