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Record W4400728583 · doi:10.1002/advs.202403387

Intron Retention of DDX39A Driven by SNRPD2 is a Crucial Splicing Axis for Oncogenic MYC/Spliceosome Program in Hepatocellular Carcinoma

2024· article· en· W4400728583 on OpenAlexaff
Cunjie Chang, Lina Li, Ling Su, Fan Yang, Quanxiu Zha, Mengqing Sun, Tao Lin, Menglan Wang, Kangli Song, Liangyu Jiang, Haojin Gao, Yexin Liang, Chao Xu, C.-C. Yong, Minmin Wang, Jiacheng Huang, Jing Liu, Weiwei Jin, Wenyuan Lv, Heng Dong, Qian Li, Fangtian Bu, Shuanghong Yan, Haoxiang Qi, Shujuan Zhao, Yingshuang Zhu, Yu Wang, Junping Shi, Yiting Qiao, Jian Xu, Benoı̂t Chabot, Jianxiang Chen

Bibliographic record

VenueAdvanced Science · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA Research and Splicing
Canadian institutionsUniversité de Sherbrooke
FundersNational Natural Science Foundation of ChinaNational Outstanding Youth Science Fund Project of National Natural Science Foundation of ChinaJinhua Science and Technology BureauZhejiang Traditional Chinese Medicine AdministrationNatural Science Foundation of Zhejiang ProvinceFundamental Research Funds for the Central UniversitiesInnovative Research Group Project of the National Natural Science Foundation of China
KeywordsSpliceosomeHepatocellular carcinomaRNA splicingIntronCancer researchBiologyGeneticsComputational biologyGeneRNA

Abstract

fetched live from OpenAlex

RNA splicing is a dynamic molecular process in response to environmental stimuli and is strictly regulated by the spliceosome. Sm proteins, constituents of the spliceosome, are key components that mediate splicing reactions; however, their potential role in hepatocellular carcinoma (HCC) is poorly understood. In the study, SNRPD2 (PD2) is found to be the most highly upregulated Sm protein in HCC and to act as an oncogene. PD2 modulates DDX39A intron retention together with HNRNPL to sustain the DDX39A short variant (39A_S) expression. Mechanistically, 39A_S can mediate MYC mRNA nuclear export to maintain high MYC protein expression, while MYC in turn potentiates PD2 transcription. Importantly, digitoxin can directly interact with PD2 and has a notable cancer-suppressive effect on HCC. The study reveals a novel mechanism by which DDX39A senses oncogenic MYC signaling and undergoes splicing via PD2 to form a positive feedback loop in HCC, which can be targeted by digitoxin.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.037
Threshold uncertainty score0.480

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.013
GPT teacher head0.309
Teacher spread0.296 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations11
Published2024
Admission routes1
Has abstractyes

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