microRNAs Regulate Cellular Magnesium by Tuning Expression of the Plasma Membrane Protein CNNM4
Bibliographic record
Abstract
High Resolution Image Download MS PowerPoint Slide Cyclin M4 (CNNM4) is a plasma membrane Mg 2+ transporter that is important for the regulation of cellular and organismal Mg 2+ homeostasis. CNNM4 is overexpressed in liver diseases, including non-alcoholic steatohepatitis and acetaminophen-induced liver injury, leading to aberrant levels of Mg 2+ . The regulatory mechanisms underlying the overexpression of this protein, however, remain unknown. Here, we demonstrate regulation of CNNM4 and cellular magnesium levels by microRNA. Using a high-throughput assay, we established the complete miRNA binding profile of the 3′UTR of the gene. Both upregulation and downregulation of CNNM4 were observed, though upregulatory activity appears more prominent. We demonstrate that in both cases, the effects arise from direct binding of the miRNAs to the CNNM4-3′UTR, and we provide direct evidence that they result in changes of cellular concentration of the metal in hepatocytes. The results reveal a potential role of microRNAs in the alteration of magnesium homeostasis in the liver through CNNM4 and, based on the miRNA proxy hypothesis, predict a broader role of CNNM4 and aberrant magnesium levels in breast cancer and other pathologies.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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) | 0.000 | 0.000 |
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 teacher head, 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".