Department of Orthopedics Spine Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830000, Xinjiang, China.
Med Oncol. 2014 Feb;31(2):821. doi: 10.1007/s12032-013-0821-3. Epub 2013 Dec 19.
MicroRNA-183 (miR-183) has been demonstrated to be a tumor suppressor miRNA in inhibition of migration and invasion of osteosarcoma by targeting an oncogene Ezrin. The aim of the present study was to determine the correlation of combined miR-183 and Ezrin mRNA expression with clinicopathologic features and prognosis in patients with osteosarcomas. Expressions of MiR-183 and Ezrin mRNA were both examined using quantitative real-time reverse transcriptase-polymerase chain reaction analysis in 68 specimens from patients with osteosarcomas. MiR-183 and Ezrin mRNA expression levels were, respectively, lower and higher in osteosarcoma tissues than those in noncancerous bone tissues significantly (both P < 0.001). Notably, the downregulation of miR-183 was negatively correlated with the upregulation of Ezrin mRNA in osteosarcoma tissues (r = -0.66, P = 0.01). In addition, the combined miR-183 downregulation and Ezrin upregulation (miR-183-low/Ezrin-high) was significantly associated with high tumor grade (P = 0.02), poor response to chemotherapy (P = 0.01), positive metastasis (P = 0.006) and recurrence (P = 0.008). Moreover, miR-183/Ezrin expression and the status of metastasis were both found to be independent prognostic factors for overall survival (P = 0.02 and 0.01, respectively) and disease-free survival (both P = 0.02). Our findings showed that the aberrant expression of miR-183 and its target gene Ezrin may play a crucial role in the development and progression of human osteosarcoma. More interestingly, the dysregulation of miR-183/Ezrin axis may be related to the prediction of aggressiveness and poor prognosis for patients with this lethal disease.
miR-183(miR-183)通过靶向癌基因 Ezrin 被证明是抑制骨肉瘤迁移和侵袭的肿瘤抑制 miRNA。本研究旨在确定 miR-183 和 Ezrin mRNA 表达的相关性与骨肉瘤患者的临床病理特征和预后的关系。使用定量实时逆转录-聚合酶链反应分析检测 68 例骨肉瘤患者标本中 MiR-183 和 Ezrin mRNA 的表达。与非癌性骨组织相比,骨肉瘤组织中 miR-183 和 Ezrin mRNA 的表达水平均显著降低(均 P < 0.001)。值得注意的是,骨肉瘤组织中 miR-183 的下调与 Ezrin mRNA 的上调呈负相关(r = -0.66,P = 0.01)。此外,miR-183 下调和 Ezrin 上调的联合表达(miR-183-low/Ezrin-high)与高肿瘤分级显著相关(P = 0.02)、对化疗反应不良(P = 0.01)、阳性转移(P = 0.006)和复发(P = 0.008)。此外,miR-183/Ezrin 表达和转移状态均被发现是总生存期(P = 0.02 和 0.01)和无病生存期(均 P = 0.02)的独立预后因素。我们的研究结果表明,miR-183 及其靶基因 Ezrin 的异常表达可能在人类骨肉瘤的发生和发展中起关键作用。更有趣的是,miR-183/Ezrin 轴的失调可能与该致命疾病侵袭性和不良预后的预测有关。