Aberrant expression of microRNA-99a and its target gene mTOR associated with malignant progression and poor prognosis in patients with osteosarcoma.
Aberrant expression of microRNA-99a and its target gene mTOR associated with malignant progression and poor prognosis in patients with osteosarcoma.
复制标题
DOI：
10.2147/ott.s102421
复制
发表时间：
2016
影响因子：
4
通讯作者：
Yang H
中科院分区：
文献类型：
--
作者：
Zhao J;Chen F;Zhou Q;Pan W;Wang X;Xu J;Ni L;Yang H
哺乳动物雷帕霉素靶蛋白（mTOR）是多种肿瘤细胞中microRNA（miR）-99a的靶基因，是骨肉瘤的独立预后标志物。本研究旨在探讨miR-99 a/mTOR轴在人骨肉瘤中的临床意义。共使用130对骨肉瘤和匹配的非癌骨组织，通过实时定量聚合酶链反应检测miR-99 a和mTOR mRNA的表达水平。统计分析miR-99 a和/或mTOR表达与骨肉瘤患者临床病理特征及预后的关系。骨肉瘤组织中miR-99 a和mTOR mRNA的表达水平分别为（2.11±1.03 vs 4.69±1.21，P<0.001）和（4.40±1.13 vs 1.74±0.85，P<0.001），低于和高于癌旁骨组织。骨肉瘤组织中miR-99 a的表达水平与mTOR mRNA的表达水平呈负相关。miR-99 a低表达和/或mTOR高表达与手术分期、转移复发和化疗疗效差相关（均P<0. 05）。此外，与miR-99 a高表达和/或mTOR低表达组相比，miR-99 a低表达和/或mTOR高表达组的骨肉瘤患者的总体生存期和无病生存期较短。多因素考克斯分析显示，miR-99 a和/或mTOR表达均为骨肉瘤的独立预后因素。我们的数据显示miR-99 a/mTOR轴在人骨肉瘤恶性进展中的关键作用，这意味着miR-99 a和mTOR的联合表达可能为这种疾病提供一种有吸引力的新的预后标志物。
The mammalian target of rapamycin (mTOR) has been reported to act as a target gene of microRNA (miR)-99a in various cancer cells and identified as an independent prognostic marker of human osteosarcoma. The aim of this study was to investigate the clinical significance of miR-99a/mTOR axis in human osteosarcoma. A total of 130 pairs of osteosarcoma and matched noncancerous bone tissues were used to detect the expression levels of miR-99a and mTOR mRNA by quantitative real-time polymerase chain reaction. Then, associations of miR-99a and/or mTOR expression with clinico-pathological features and prognosis of patients with osteosarcoma were statistically analyzed. The expression levels of miR-99a (tumor vs normal: 2.11±1.03 vs 4.69±1.21, P<0.001) and mTOR mRNA (tumor vs normal: 4.40±1.13 vs 1.74±0.85, P<0.001) in osteosarcoma tissues were, respectively, lower and higher than those in noncancerous bone tissues. The expression levels of miR-99a in osteosarcoma tissues were negatively correlated with those of mTOR mRNA. Additionally, miR-99a-low and/or mTOR-high expression were all significantly associated with advanced surgical stage, positive metastasis and recurrence, and poor response to chemotherapy (all P<0.05). Moreover, patients with osteosarcoma with miR-99a-low and/or mTOR-high expression had shorter overall and disease-free survivals than those in miR-99a-high and/or mTOR-low expression groups. Multivariate Cox analyses showed that miR-99a and/or mTOR expression were all independent prognostic factors of osteosarcoma. Our data showed the crucial role of miR-99a/mTOR axis in the malignant progression of human osteosarcoma, implying that conjoined expression of miR-99a and mTOR may offer an attractive novel prognostic marker for this disease.