人甲状腺乳头状癌的环状RNA表达谱研究  

Study of circular RNA expression profile in human papillary thyroid carcinoma

作　　者：李姗姗[1] 郭敏[2] 王严[2] 宋玲玲 马翠[3] 陆萍 Li Shanshan;Guo Min;Wang Yan;Song Lingling;Ma Cui;Lu Ping(Department of Biopharmaceutical Sciences,College of Pharmacy,Harbin Medical University,Harbin 150081,China)

机构地区：[1]哈尔滨医科大学药学院生物制药教研室,150081 [2]哈尔滨医科大学附属第四医院内分泌科,150081 [3]哈尔滨医科大学大庆校区免疫教研室,163000

出　　处：《国际遗传学杂志》2018年第5期348-354,共7页International Journal of Genetics

基　　金：黑龙江省教育厅科学技术研究项目（12541445）

摘　　要：目的为探讨甲状腺乳头状癌（papillary thyroid carcinoma，PTC）的发病机制，采用基因芯片技术，分析circular RNAs（circRNAs）在甲状腺乳头状癌及其癌旁组织中的表达谱差异及临床意义。方法收集3例手术切除的甲状腺乳头状癌组织及对应癌旁组织，采用基因芯片技术分别检测其circRNA表达谱，并进行组间比较与分析，以明确差异表达的circRNA，根据差异倍数选取差异最为显著的10个circRNA，采用定量RT-PCR（quantitative reverse transcription PCR，RT-qPCR）方法验证其在50对PTC患者及正常人全血中的表达情况。采用Arraystar公司circRNA靶基因分析软件，预测可能与上/下调明显的circRNA相互作用的靶miRNA分子。结果与癌旁组织相比，甲状腺乳头状癌组织的circRNA表达谱存在明显差异。在表达差异最显著的10个circRNAs中，其表达上调或下调的差异倍数均超过2.5倍（3个上调，7个下调），经RT-qPCR验证结果显示，与癌旁组织相比，甲状腺乳头癌组织中hsa_circRNA_074595表达上调3.91±0.13倍（P＝0.045），hsa_circRNA_100778下调3.61±0.05（P＝0.007），hsa_circRNA_104348下调4.47±0.17倍（P＝0.003）；circRNA靶基因分析软件预测结果提示：miR-3944、-4435、-3467、-146、-92、-519和-301可能是hsa_circRNA_074595、_100778和_104348的潜在靶基因。结论circRNA芯片可用于筛选甲状腺乳头状癌组织中差异表达的circRNA，与癌旁组织相比，多种circRNA在甲状腺乳头状癌组织中呈异常表达，这些circRNA及其潜在的靶基因可能与甲状腺乳头状癌的发生发展密切相关。ObjectiveTo study the pathogenesis of papillary thyroid carcinoma （PTC）, human circular RNAs （circRNAs） microarray was used to analyze circRNAs profile in PTC tumor and mated adjacent tissues. Their clinical significance in PTC were also indicated from the chip assay.MethodsThree cases of surgical excision of PTC and corresponding para cancerous tissue were collected for human circRNA microarray. The differential expression of circRNAs between the two groups were clarified by comparison and analysis of the circRNA expression profile. Among these circRNAs, 10 circRNAs that were most significantly upregulated or downregulated were selected for quantitative reverse transcription PCR （RT-qPCR）identification in plasma from 50 pairs of PTC patients and controls. The circRNA/microRNA interaction was also predicted with Arraystar’s home-made miRNA target prediction software.ResultsCompared with adjacent tissues, the expression profile of circRNA in PTC were significantly different. Among these, 10 circRNAs were most significantly upregulated or downregulated, which were dysregulated by more than 2.5 times （3 upregulated and 7 downregulated）. RT-qPCR verified 3 positive dysregulated circRNAs subsequently, which hsa_circRNA_074595 was upregulated by 3.91±0.13 times （P=0.045）, while hsa_circRNA_100778 and hsa_circRNA_104348 were downregulated by 3.61±0.05 times （P=0.007） and 4.47±0.17 times （P=0.003）, respectively. The circRNA/microRNA prediction indicated that miR-3944, -4435, -3467, -146, -92, -519 and -301 may be potential targets of hsa_circRNA_074595, _100778 and_104348.ConclusionscircRNA microarray screening can be used to detect the differential circRNA expression of PTC and these dysregulated circRNAs and their potential target genes may play an important role in the development of PTC.

关 键 词：甲状腺乳头状癌 环状RNA 芯片 非编码RNA 

分 类 号：R736.1[医药卫生—肿瘤]