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With Technology Developed at UM, Non-Profit MiRcore Provides miRNA Research Support

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By Doug Macron

Aiming to fill a gap in the microRNA research field, non-profit startup MiRcore is on the lookout for collaborators interested in working with its proprietary miRNA target-prediction technology.

According to MiRcore Founder and President Inhan Lee, the organization is an outgrowth of her time as an investigator at the University of Michigan, where she saw “many people … [doing] microRNA research, but without any good support.”

Initially, she envisioned an miRNA core facility within the university, but realized that many of her collaborators who could benefit from such support were at other institutions, some of which were overseas, and not eligible for such a resource, she told Gene Silencing News.

Instead, she established MiRcore in mid-2009. Its core technology, developed by Lee at UM and exclusively licensed to the organization, is based on the discovery of a new class of miRNA targets, dubbed miBridge, that contain both 5' UTR and 3' UTR interaction sites.

According to a paper Lee and colleagues published in Genome Research, while miRNAs “post-transcriptionally regulate target mRNAs through the 3' UTR, which interacts mainly with the 5' end of [miRNAs] in animals … [there are] many endogenous motifs within human 5' UTRs specific to the 3' ends of miRNAs.

“The 3' end of conserved miRNAs, in particular, has significant interaction sites in the human-enriched, less-conserved 5' UTR miRNA motifs, while human-specific miRNAs have significant interaction sites only in the conserved 5′-UTR motifs, implying both miRNA and 5′-UTR are actively evolving in response to each other,” the study's authors wrote. “Additionally, many miRNAs with their 3' end interaction sites in the 5' UTRs turn out to simultaneously contain 5' end interaction sites in the 3' UTRs.”

In the paper, the team demonstrated “combinatory interactions” between single miRNAs and both end regions of an mRNA, and showed that “genes exhibiting large-scale protein changes due to miRNA over-expression or deletion contain both UTR interaction sites predicted.”

These findings led Lee to develop an miRNA target-prediction method with increased specificity for miRNA targets that examines both 5' UTR interactions, as well as the conventional 3' UTR interactions. Looking at 3' UTRs alone can often result in “a high number” of false positives, according to MiRcore.

“It turns out that most known miRNAs have potential miBridge targets, and most known genes have potential miBridge regulating miRNAs, essentially covering the whole genome,” the non-profit states on its website.

In addition to offering its collaborators access to its miBridge miRNA target-prediction approach, MiRCore also offers a technology, called mirFilter, for identifying key miRNAs in a system of interest based solely on gene-expression data.

Although Lee declined to provide specific details about mirFilter before related data are published, MiRcore said that experiments using the approach identified miR-200a, miR-223, and miR-335 in a comparison of metastatic and non-metastatic cancer cell line data.

“Confirming the validity of this method, previously only miR-200a and miR-335 had already been found to be anti-metastatic miRNAs,” according to the organization. “The specificity of the result makes the case for testing the hypothesis that miR-223 is another anti-metastatic miRNA,” a conclusion that was validated in a collaborator's lab.

Lee said that, at this stage, all of MiRcore's collaborators are academic, and that the organization's goal is primarily to publish high-quality research papers.

New collaborators provide two sets of up-regulated and down-regulated mRNA and miRNA profiling data, and receive from MiRcore predicted miRNA/mRNA target networks, including novel miRNA target candidates. “Normally, fewer than 10 miRNA/mRNA target gene pairs are identified through this process,” which provides researchers with a manageable number of potential targets for validation within their own labs, the non-profit states.


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