High Expression Of MicroRNA-100 Is Associated With Lymph Node Metastasis,TNM Stage And Diffferentiation Grade In Colorectal Cancer

BackgroundsStatistics indicate that CRC incidence is markedly increasing in china. Although the treatment have improved rapidly, CRC characterized with high invasion and metastasis, still remains the second leading cause of cancer-related deaths. Up to 30% of patients with CRC will inevitably developed into metastasis disease under natural conditions, of those the average survival time is less than 30 months.MicroRNAs (miRNAs), a class of small, highly conserved, endogenously expressed and noncoding RNAs, can regulate the translation or degradation of mRNAs by binding to its 3’untranslated regions (3’UTR), resulting in changes of cellular malignant behaviors.ObjectiveThe aim of this study was to investigate the expression of miR-100 and its potential function to detect early metastasis and to predict tumor malignancy in Colorectal Cancer (CRC).MethodsThe expression of miR-100 was examined by quantitative real-time PCR (qRT-PCR) in 172 CRC tissues. The association of miR-100 expression patterns with lymph node metastasis, differentiation grade and tumor-node-metastasis (TNM) stage of CRC was analyzed. Manipulation of miR-100 expression and its consequences in CRC cellular proliferation, apoptosis and migration were demonstrated in vitro models.ResultsThe results indicated that the expression of miR-100 was downregulated in colorectal cancer specimens with or without lymph node metastasis compared to adjacent normal tissues respectively (P<0.01). However, the expression level of miR-100 in CRC tissues with lymph node metastasis was higher than those without lymph node metastasis(P<0.01). Furthermore, the expression of miR-100 was increased progressively from TNM stage I to stage IV (P<0.01) and from well differentiation grade to poor differentiation grade (P< 0.01). There was no significant correlation between miR-100 expression and overall survival rates of CRC patients (P=0.179, log-rank test). Univariate analysis with Cox proportional hazards model showed that differentiation grades, lymph node metastasis and TNM stages were statistically prognostic factors. Multivariate analysis of the prognostic factors with Cox proportional hazards model confirmed that differentiation grades (P <0.01) and TNM stages (P<0.01) were significant independent predictor of poor survival in CRC patients. Overexpression of miR-100 in CRC cell line HCT-8 inhibited cellular proliferation, promoted cellular apoptosis and migration.ConclusionOur findings indicated that the expression of miR-100 could reflect the malignancy of CRC in lymph node metastasis, TNM stage and differentiation grade, and may be a potential therapeutic target in CRC patients.