406933

MIR141

MIRN141;microRNA 141;MIR141;microRNA 141

hsa-mir-141

12p13.31

ncRNA

microRNAs (miRNAs) are small noncoding RNAs which play essential roles in many important biological processes. Therefore, their dysfunction is associated with a variety of human diseases, including cancer. Increasing evidence shows that miRNAs can act as oncogenes or tumor suppressors, and although there is great interest in research into these cancer-associated miRNAs, little is known about them. In this study, we performed a comprehensive analysis of putative human miRNA oncogenes and tumor suppressors. We found that miRNA oncogenes and tumor suppressors clearly show different patterns in function, evolutionary rate, expression, chromosome distribution, molecule size, free energy, transcription factors, and targets. For example, miRNA oncogenes are located mainly in the amplified regions in human cancers, whereas miRNA tumor suppressors are located mainly in the deleted regions. miRNA oncogenes tend to cleave target mRNAs more frequently than miRNA tumor suppressors. These results indicate that these two types of cancer-associated miRNAs play different roles in cancer formation and development. Moreover, the patterns identified here can discriminate novel miRNA oncogenes and tumor suppressors with a high degree of accuracy. This study represents the first large-scale bioinformatic analysis of human miRNA oncogenes and tumor suppressors. Our findings provide help for not only understanding of miRNAs in cancer but also for the specific identification of novel miRNAs as miRNA oncogenes and tumor suppressors. In addition, the data presented in this study will be valuable for the study of both miRNAs and cancer.

BACKGROUND: We have demonstrated that T lymphoma invasion and metastasis 1 (Tiam1) gene is associated with the poor prognosis of patients with hepatocellular carcinoma (HCC), and we used a computational approach to identify miR-141 as a Tiam1-targeting microRNA (miRNA). Here, we explored the function of miR-141 and the relationship between miR-141 and Tiam1 gene in HCC. METHODS: The miR-141 expression in HCC tissues and cell lines was detected and its roles in regulation of HCC cell proliferation, migration and invasion and target gene expression was investigated. Tiam1 was identified as a novel target of miR-141. Ethics statement: our study was approved by the Nanfang Hospital Medical Ethics Committee Ethics statement. Written informed consent was obtained before collection. RESULTS: Based on in situ hybridization (ISH) analysis, miR-141 was down-regulated in the same HCC samples. Kaplan-Meier analysis demonstrated that patients with low miR-141 expression had poorer overall survival rate than that of the patients with high miR-141 expression. Furthermore, multivariate Cox regression analysis indicated that miR-141 could serve as an independent prognostic factor in HCC. MiR-141 significantly inhibited in vitro cell proliferation, migration and invasion as proved by gain- and loss- of function studies, while the mRNA and protein levels of Tiam1 were reduced in cells over-expressing miR-141. Moreover, Tiam1 treatment antagonized this effect, while knockdown of Tiam1 by Tiam1 short hairpin RNA (shTiam1) induced inhibitory effects. CONCLUSIONS: These findings indicated that miR-141 functions as a tumor suppressor and inhibits the migration and invasion of HCC cells by targeting Tiam1, which may provide novel prognostic and treatment strategies for HCC patients.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Increasing evidence suggests that microRNAs (miRNAs) are associated with HCC tumorigenesis. The present study was designed to define the role of miR-141 in HCC. The expression of miR-141 was significantly decreased in four HCC cell lines. Overexpression of miR-141 suppressed both the growth and the motility of HCC cells. Furthermore, we identified zinc finger E-box binding homeobox 2 (ZEB2) as a target of miR-141 and miR-141 functioned as a tumor suppressor via ZEB2 targeting in HCC. These data provide a novel potential therapeutic target for HCC treatment.