407054

MIR98

MIRN98|hsa-mir-98|miR-98;microRNA 98;MIR98;microRNA 98

-

Xp11.22

miscRNA

Count: 2; Pubmed_search,Generif

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.

FUS1 is a tumor suppressor gene located on human chromosome 3p21, and expression of Fus1 protein is highly regulated at various levels, leading to lost or greatly diminished tumor suppressor function in many lung cancers. Here we show that selected microRNAs (miRNA) interact with the 3'-untranslated region (3'UTR) of FUS1, leading to down-regulation of protein expression. Using computational methods, we first predicted that FUS1 is a target of three miRNAs, miR-93, miR-98, and miR-197, and then showed that exogenous overexpression of these miRNAs inhibited Fus1 protein expression. We then confirmed that the three miRNAs target the 3'UTR region of the FUS1 transcript and that individual deletion of the three miRNA target sites in the FUS1 3'UTR restores the expression level of Fus1 protein. We further found that miR-93 and miR-98 are expressed at higher levels in small-cell lung cancer cell lines (SCLC) than in non-small-cell lung cancer cell lines (NSCLC) and immortalized human bronchial epithelial cells (HBEC), and that miR-197 is expressed at higher levels in both SCLCs and NSCLCs than in HBECs. Finally, we found that elevated miR-93 and miR-197 expression is correlated with reduced Fus1 expression in NSCLC tumor specimens. These results suggest that the three miRNAs are negative regulators of Fus1 expression in lung cancers.