miR-134在无功能垂体腺瘤中的表达及其与肿瘤增殖侵袭能力的关系

The down--regulation of miR-134 expression in clinically non- functional pituitary adenomas and its effects on tumor proliferation and invasiveness

目的检测miR-134在正常垂体组织和各垂体腺瘤亚型中的表达情况，分析其表达水平与无功能垂体腺瘤（NFPA）增殖侵袭能力的相关性。方法收集垂体腺瘤标本52例（NFPA33例，PRL腺瘤5例，GH腺瘤9例，ACTH腺瘤5例）和尸检正常腺垂体4例及临床相关病例资料，利用免疫组织化学、实时荧光定量PCR（qRT—PCR）等实验技术检测miR-134、MEG3和Ki-67等在各标本中的表达量，并结合病例资料分析数据。结果mIR-134在NFPA中表达水平明显低于其他类型垂体腺瘤和正常腺垂体（P〈0．01）；并且miR-134的表达水平与NFPA患者发病年龄、肿瘤细胞Ki-67阳性率及肿瘤侵袭性呈负相关（P〈0．01）。结论miR-134表达下调可能是NFPA肿瘤发生及肿瘤呈侵袭样生长的重要原因之一；miR-134有望成为用于NFPA诊疗的新靶点。

Objective To investigate the expression of miR-134 in pituitary normal tissues and all types of pituitary adenomas and to assess the relationship between its expression level and clinically non--functioning pituitary adenoma （NFPA） cells＇ proliferation and invasiveness. Methods Sporadic pi- tuitary adenoma specimens （ n =52,NFPA 33,PRL 5,GH 9 and ACTH 5） with their clinical data and normal pituitary glands （ n = 4） were collected from autopsy. The expression of miR--134, MEG3 and Ki--67 were quantitatively examined using immunohistochemistry and quantitative real--time reverse transcriptase polymerase chain reaction techniques. The differential expression of miR--134 and MEG3 in pituitary normal and tumor tissues and the association of miR-- 134 expression with NFPA tumor cells＇ proliferation and invasiveness were evaluated by statistical tests. Results The expression level of miR-- 134 in NFPA was extremely lower than that in pituitary normal tissues and other types of pituitary adenomas （P ~ 0.01）. Moreover, the expression level of miR--134 in NFPA was negatively correlated to the age at diagnosis （P = 0. 027）, the percentage of Ki--67 in NFPA tissues （P % 0. 001） and tumor invasiveness （P -- 0. 008）. Conclusions The down--regulation of miR--134 expression may lead to the tumorigenesis of NFPA and contribute to tumor cells＇ high proliferation and the phenotype of invasive- ness. Consequently, miR--134 may become a novel biomarker for the diagnosis and a potential therapeu- tic target for the treatment of NFPA in the future.