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Small But Useful: microRNAs for Diagnostics and Therapeutics

miRTarBase: a database curates experimentally validated microRNA-target interactions
Nucleic Acids Res. 2014 Jan;42(Database issue):D78-85. Fig. 2&3
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miRTarBase: a database curates experimentally validated microRNA-target interactions Nucleic Acids Res. 2014 Jan;42(Database issue):D78-85. Fig. 2&3 ...

MicroRNA (miRNA) is a small non-coding RNA molecule which is widely found in organisms such as nematodes, fruit flies, mammals and plants. In 1993, researchers first discovered miRNA in the research on Caenorhabditis elegans. Until now around 28,645 miRNAs have been discovered from different species, and about 2,588 miRNAs are inside human body. Recent studies shown miRNA could be the biomarkers for diagnosis and the drug for therapeutics.

One of the major functions of miRNA is to regular gene activity by suppressing protein synthesis or inducing the degradation messenger RNA (mRNA). Many biological processes are regulated by miRNA such as cell growth, cell differentiation, embryo development and disease progression. Because of the importance of miRNAs in regulating gene expressions, the 2006 Nobel Prize in Physiology or Medicine was awarded to Andrew Fire and Craig C. Mello for recognizing their research on RNA interference (RNAi). Now through the RNAi technique and bioinformatics tools, researchers could figure out the functional roles of genes with specific miRNA. A good example is miR-122 which specifically expressed in liver and associated with liver cancer. With these new techniques, researches not only showed that miR-122 was involved in modulation of lipid metabolism, hepatitis C virus replication and anti-apoptosis, but also found that more and more miR-122 target genes could be the possible cure for inhibiting tumor progression. Currently, some miRNA drugs undergo clinical trials. For example, MRX34, a miR-34 mimic, is the first cancer-targeted miRNA drug against advanced hepatocellular carcinoma and its phase I clinical study would be completed in the first quarter of 2015. Researchers believe that these promising miRNA drugs would be in clinical use soon.

Most of the miRNAs in human body is inside the cells, but a small amount of them are circulating freely in the blood. These miRNAs which are called circulating miRNA might come from dying cells or the secretion of normal cells. Circulating miRNAs offer an alternative approach when diagnosing diseases, such as preeclampsia and hepatocellular carcinoma. Furthermore, miRNAs are highly related to prognosis of cancers such as breast cancer and ovarian cancer. Hence, to establish a panel of miRNA biomarkers achieving simultaneous detection of expression variation is helpful in diagnostics and prognostics in various diseases.

Dr. Hsien-Da Huang’s research team in National Chiao Tung University established a series of miRNA databases, computational tools and integrated analysis platforms, which have been applying in various studies, especially in diagnosis and therapeutic. The database, miRTarBase, which is the world-class miRNA-Target interaction (MTI) database providing extensive experimental support in all miRNA-related research. Another database, miRStart, which is used to predict miRNA transcription start site (TSS). With miRNA TSS and miRNA target genes information, researchers could both reconstruct miRNA regulatory network and find miRNA-associated diseases. An analysis tools called MicroRNA Target Prediction (miRTar) which enables biologists to identify the biological functions and regulatory relationships between a group of known/putative miRNAs and protein coding genes. It can identify the crucial miRNAs which could be biomarkers for cancer diagnosis and suppress the cancer-promoting genes.

Because of the advance of next generation sequencing (NGS) technology, it is getting easy to quantify miRNA, to identify new miRNAs and to verify the miRNA-target interactions. When both regulatory networks of miRNAs and miRNA target genes are identified, we could clarify the detailed interaction mechanisms. Now, it becomes more useful in therapeutics and disease prevention.


Updated : 2021-09-28 12:14 GMT+08:00