The Dual Role of RASSF4 in Tumorigenesis: Mechanisms and Epigenetic Targeting Strategies
Bibliographic record
Abstract
RASSF4 is a key member of the Ras-associated domain family (RASSF) that exhibits dual functionality in tumorigenesis, playing critical yet context-dependent roles in various malignancies. Its expression is epigenetically regulated through promoter hypermethylation, histone modifications, and microRNAs including miR-155 and miR-196a-5p, which directly target its 3' untranslated region. In most cancers, such as non-small cell lung cancer (NSCLC) and gastric adenocarcinoma (GAC), RASSF4 acts as a tumor suppressor by inhibiting the RAS/MAPK pathway while activating the Hippo signaling cascade, ultimately inducing cell cycle arrest and apoptosis. Conversely, in aRMS, RASSF4 is upregulated by the PAX3-FOXO1 fusion oncoprotein and promotes tumor growth through MST1 inhibition and subsequent YAP activation. This review systematically analyzes current evidence regarding RASSF4's complex regulatory mechanisms and clinical significance. We propose targeted therapeutic strategies including epigenetic reactivation, gene intervention, and combination therapies. Furthermore, we identify RASSF4 as a promising diagnostic biomarker and therapeutic target based on integrated mechanistic and clinical evidence. Future research should focus on elucidating context-dependent regulatory switches, developing targeted delivery systems, and validating clinical utility through prospective trials.
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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) | 0.001 | 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".