ZDHHC12 Palmitoylates HDAC8 to Promote the Progression of Hepatocellular Carcinoma Associated with a Diet High in Saturated Fatty Acids
Bibliographic record
Abstract
Excessive intake of saturated fatty acids (SFAs)-commonly associated with diets rich in fried foods and red meat-significantly increases the risk of hepatocellular carcinoma (HCC). Palmitic acid (PA), the most prevalent type of SFA, is selected as the representative model for this study. Palmitoyltransferases play crucial roles in protein palmitoylation mediated by PA; however, the most significantly altered palmitoyltransferase under high-SFA dietary conditions remains unidentified. This study reveals zinc finger DHHC-type palmitoyltransferase 12 (ZDHHC12) as a key protein in PA-driven HCC progression that functions by stabilizing the oncogenic histone deacetylase 8 (HDAC8). Mechanistically, PA supplementation upregulates ZDHHC12 expression by activating the transcription factor SWI/SNF-related BAF chromatin remodeling complex subunit ATPase 4 (SMARCA4). ZDHHC12 mediates HDAC8 palmitoylation at cysteine 244, thereby inhibiting its lysosomal degradation and ultimately promoting HCC progression. This study reveals that ZDHHC12 is a critical mediator of PA-induced HCC progression and that targeting HDAC8 can suppress this process. These findings offer a potential therapeutic strategy for HCC patients with high dietary intake of SFAs, particularly PA.
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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 | 0.001 |
| 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".