Abstract 3203: Extravasation and metastasis dynamics are cytoplasmically controlled by the epitranscriptome
Bibliographic record
Abstract
Abstract Non-coding RNA (ncRNA) and RNA binding proteins (RBPs) primarily reside in the nucleus to regulate splicing, transcription, and transcript stability. However, their role(s) in the cytoplasm were unclear until now. Evidence now suggests that ncRNAs within the cytoplasm play an important role in cancer invasion. In concert with MT1-MMP, a protease involved in invadopodia formation, long non-coding RNAs (lncRNAs) and RBPs form cytoplasmic complexes with MT1-MMP, which we termed “R-bodies” and are abundant in invasive breast cancer cells. RNA immunoprecipitation sequencing (RIP-seq) of only the cytoplasm identified the RNA at the core of these complexes to be metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a lncRNA which has been previously described as playing a fundamental role in cancer but only within the nucleus. Further investigation revealed that R-body-associated-MALAT1 was m6A-epigenetically marked. Depletion of any component of R-bodies and inhibition of m6A epigenetic marking of MALAT1 halted R-body formation and subsequent cell invasion. Importantly, we demonstrate that this cytoplasmic complex can be functionally targeted using RNA therapy against m6A-MALAT1 as well as drugs which inhibit the methyltransferase responsible for the m6A methylation of MALAT1. The identification of R-bodies has far-reaching implications and links the roles of cytoplasmic ncRNA and RBPs to the progression of disease. Citation Format: Olivia R. Grafinger, Gobi Thillainadesan, Boyang Su, Yulin Mo, Xin Xu, Sara Mar, Minzhi Sheng, Sumaitha Al Islam, Jennifer Geddes-McAllister, Marc G. Coppolino, Hansen H. He, Gang Zheng, Katarzyna J. Jerzak, Hon S. Leong. Extravasation and metastasis dynamics are cytoplasmically controlled by the epitranscriptome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3203.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".