Ke Tao-Wei, Wei Po-Li, Yeh Ken-Tu, Chen William Tzu-Liang, Cheng Ya-Wen
Institute of Medicine, Chung-Shan Medical University, Taichung, Taiwan.
Ann Surg Oncol. 2015 Aug;22(8):2649-55. doi: 10.1245/s10434-014-4305-2. Epub 2014 Dec 17.
MicroRNAs regulate gene expression at the posttranscriptional level and play important roles in tumor development, progression, and metastasis. The aim of this study was to investigate the role of microRNA-92a (miR-92a) in metastasis of colorectal cancer (CRC).
One hundred fifty-eight CRC patients were enrolled. The expression of miR-92a, PTEN, and E-cadherin was analyzed by real-time PCR. Univariate (Kaplan-Meier) analysis was used to analyze primary outcomes included 5-year overall survival and tumor recurrence. CRC cell model studies were used to analyze the miR-92a-involved CRC metastasis.
The expression of miR-92a in tumor tissues was significantly positively correlated with lymph node metastasis in CRC patients (p = 0.012). After adjusting for age, sex, and disease differentiation, this correlation remained significant (p = 0.01). In addition, there was a negative correlation between levels of miR-92a and the PTEN gene (p < 0.0001). No any association of miR-92a and E-cadherin was found (p = 0.128). Patients with high miR-92a/low PTEN had poorer overall survival and disease-free survival rates than those with high miR-92a/high PTEN, low miR-92a/high PTEN, and low miR-92a/low PTEN. The association of levels of miR-92a and PTEN with tumor cell migration in CRC was also confirmed in CRC cell models.
We suggest that miR-92a is involved in lymph node metastasis of CRC patients through PTEN-regulated PI3K/AKT signaling pathway.
微小RNA在转录后水平调控基因表达，在肿瘤发生、发展及转移过程中发挥重要作用。本研究旨在探讨微小RNA-92a（miR-92a）在结直肠癌（CRC）转移中的作用。
纳入158例CRC患者。采用实时定量PCR分析miR-92a、PTEN和E-钙黏蛋白的表达。采用单因素（Kaplan-Meier）分析评估包括5年总生存率和肿瘤复发在内的主要结局。通过CRC细胞模型研究分析miR-92a参与的CRC转移。
CRC患者肿瘤组织中miR-92a的表达与淋巴结转移显著正相关（p = 0.012）。在调整年龄、性别和疾病分化后，这种相关性仍然显著（p = 0.01）。此外，miR-92a水平与PTEN基因呈负相关（p < 0.0001）。未发现miR-92a与E-钙黏蛋白有任何关联（p = 0.128）。与高miR-92a/高PTEN、低miR-92a/高PTEN和低miR-92a/低PTEN的患者相比，高miR-92a/低PTEN的患者总生存率和无病生存率较差。CRC细胞模型也证实了miR-92a和PTEN水平与CRC肿瘤细胞迁移的相关性。
我们认为miR-92a通过PTEN调控的PI3K/AKT信号通路参与CRC患者的淋巴结转移。
