Differential Expression of Mirna* Species in Cancer and the Contribution of MiR-223* to the Development of Acute Myeloid Leukemia.
Bibliographic record
Abstract
Abstract Abstract 2960 Poster Board II-936 Processing of the pre-miRNA through Dicer1 generates a miRNA duplex, consisting of a miRNA and miRNA* strand. While the functional roles of miRNAs are now well established, the potential roles of miRNA* species remain unclear. However, recent evidence suggests that the star strand of some miRNAs can be abundant and enter the RISC complex. Since the abundance of miRNA*s has not been comprehensively assessed in mammals and we took advantage of 10 deep sequencing libraries from a variety of human and murine cells to determine the most abundant complementary strand for non-annotated miRNA*s. We then calculated the ratio of miRNA/miRNA* for each miRNA duplex. In contrast to previous assumptions that one strand is highly dominant, we found that approximately 50% of the investigated miRNA duplexes exhibit high ratios with a dominating strand (ratio >100), 20% have intermediate ratios (ratio between 100-10) and a remarkable 10% show low ratios (ratio <10), indicating comparable expression of both strands. In addition, we found that ∼10% of all miRNA/miRNA* duplexes display inverse ratios (ratio<1), indicating incorrect annotation in miRBase. Comparing miRNA/miRNA* ratios across the miRNA sequence libraries revealed that most ratios remain constant across tissues and species. This could possibly allow for a novel classification of miRNAs into a-duplexes, miRNAs duplexes with a dominant strand and b-duplexes with both strands being abundant. However, certain ratios were highly variable across the libraries examined as exemplified for the ratio of miR-223/miR-223* which ranged from 0.11 (317:2684 read counts) to 19.6 (13006:660 read counts) in murine and human leukemia cell lines. Bioinformatics analysis on predicted miR-223* targets showed an enrichment for cancer associated genes (p<0.05), suggesting a tumor suppressor-like role for miR-223. Consistent with this, an analysis of samples from 94 AML patients with normal karyotype revealed an inverse correlation of miR-223* with CD34 expression (p=0.018), a negative prognostic marker in AML. In addition, in vitro experiments with mutated miR-223 and miR-223* constructs revealed regulatory potential for miR-223* in myeloid progenitor cells. Taken together, we propose a new classification for miRNA duplexes and provide evidence for a possible role a miRNA* in the development of acute myeloid leukemia. Disclosures: No relevant conflicts of interest to declare.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".