长链非编码RNA-AK017233在乌拉坦诱导的小鼠肺癌组织中低表达

摘要

OBJECTIVE To explore the dyna mic change of lncRNA expression during lung carcino-genesis induced by urethane.METHODS A total of 40 BALB/c mice received weekly ip injection of urethane 1 g·kg -1 for four continuous weeks,mice were euthanized at 12th week or 24th week after the first urethane treat ment,respectively.The RNA of lung tissues were isolated and used for microarray analysis.Based on the results of the microarray we selected lncRNA-AK017233 for additional qPCR analysis in individual mouse.RESULTS The incidence of lung cancer were 85% and 100% at 12th week and 24th week after the first ad ministration of urethane,respectively.The multiplicity and dia meter of lung tu mors in 24 weeks treated group were statistically significant fro m those in 12 weeks treated group (P<0.01 ),and pathological analysis showed that tu mors were classifiable as moderately differ-entiated adenocarcino ma.Total of 26 Down-regulated lncRNAs in which lncRNA-AK017233 stand for the most down-regulated lncRNA were identified by microcarray analysis.qPCR detected that the lncRNA-AK017233 was significantly altered by 0.33 ti mes in lung tu mors of urethane treated group at 12th week, co mpared to parallel lung tissues in urethane treated group at 12th week.AK017233 expression of ure-thane treated group was significantly reduced by 0.22 ti mes at 24th week,co mpared to parallel lung tis-sues in urethane treated group at 24th week.CONCLUSION LncRNA-AK017233 was consistently down-regulated during urethane induced lung carcinogenesis.%目的：探寻乌拉坦诱导肺癌形成过程中 lncRNA 表达的动态变化过程。方法BALB/c 小鼠每周 ip 给予乌拉坦1 g·kg -1，连续4周，分别在处理后第12周或第24周处死。分离小鼠肺组织，提取 RNA。通过长链非编码 RNA 芯片和定量 PCR 的方法分析长链非编码 RNA-AK017233表达。结果与对照组相比，乌拉坦染毒12周后的小鼠肺肿瘤的发生率为85％，每只小鼠平均肿瘤数为2．81±2．04，肿瘤的平均大小为（0．68±0．20）mm；乌拉坦染毒24周后的小鼠肺肿瘤的发生率为100％，每只小鼠平均肿瘤数为6．00±2．07，肿瘤的平均大小为（1．76±1．34）mm。病理检查显示均为肺腺癌。乌拉坦处理的确可以影响小鼠肺组织内的长链非编码 RNA 表达情况。通过芯片分析，发现以长链非编码 RNA-AK017233为代表的26个表达下调的长链非编码 RNA，随后通过定量 PCR 确认长链非编码 RNA-AK017233在乌拉坦处理12周诱发的肺腺癌组织中表达水平下调33％，在乌拉坦处理24周诱发的肺腺癌组织中表达水平下调22％。结论长链非编码 RNA-AK017233在乌拉坦诱导的肺癌形成过程中始终处于低表达状态。