MétaCan
Menu
Back to cohort
Record W4221039064 · doi:10.1038/s41467-022-29016-x

The aberrant upregulation of exon 10-inclusive SREK1 through SRSF10 acts as an oncogenic driver in human hepatocellular carcinoma

2022· article· en· W4221039064 on OpenAlexafffund
Cunjie Chang, Muthukumar Rajasekaran, Yiting Qiao, Heng Dong, Yu Wang, Hongping Xia, Amudha Deivasigamani, Minjie Wu, Karthik Sekar, Hengjun Gao, Mengqing Sun, Yuqin Niu, Qian Li, Tao Lin, Z. Yan, Menglan Wang, Shasha Chen, Shujuan Zhao, Dajing Chen, Lina Li, Fan Yang, Haojin Gao, Baodong Chen, Ling Su, Liang Xu, Ye Chen, Veerabrahma Pratap Seshachalam, Gongxing Chen, Jayantha Gunaratne, Wanjin Hong, Junping Shi, Gongying Chen, David S. Grierson, Benoı̂t Chabot, Tian Xie, Kam M. Hui, Jianxiang Chen

Bibliographic record

VenueNature Communications · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA Research and Splicing
Canadian institutionsUniversité de SherbrookeUniversity of British Columbia
FundersNatural Science Foundation of Zhejiang ProvinceCanadian Institutes of Health ResearchNational Natural Science Foundation of ChinaNational Medical Research CouncilMedical Research CouncilServier
KeywordsExonRNA splicingAlternative splicingSplicing factorBiologyNonsense-mediated decayCancer researchRegulatorMinigeneDownregulation and upregulationSR proteinRNA-binding proteinCell biologyMessenger RNAMolecular biologyGeneRNAGenetics

Abstract

fetched live from OpenAlex

Abstract Deregulation of alternative splicing is implicated as a relevant source of molecular heterogeneity in cancer. However, the targets and intrinsic mechanisms of splicing in hepatocarcinogenesis are largely unknown. Here, we report a functional impact of a Splicing Regulatory Glutamine/Lysine-Rich Protein 1 (SREK1) variant and its regulator, Serine/arginine-rich splicing factor 10 (SRSF10). HCC patients with poor prognosis express higher levels of exon 10-inclusive SREK1 (SREK1 L ). SREK1 L can sustain BLOC1S5-TXNDC5 (B-T) expression, a targeted gene of nonsense-mediated mRNA decay through inhibiting exon-exon junction complex binding with B-T to exert its oncogenic role. B-T plays its competing endogenous RNA role by inhibiting miR-30c-5p and miR-30e-5p, and further promoting the expression of downstream oncogenic targets SRSF10 and TXNDC5. Interestingly, SRSF10 can act as a splicing regulator for SREK1 L to promote hepatocarcinogenesis via the formation of a SRSF10-associated complex. In summary, we demonstrate a SRSF10/SREK1 L /B-T signalling loop to accelerate the hepatocarcinogenesis.

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 score0.472
Threshold uncertainty score0.692

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0000.001
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 head0.021
GPT teacher head0.330
Teacher spread0.309 · 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

Citations78
Published2022
Admission routes2
Has abstractyes

Explore more

Same venueNature CommunicationsSame topicRNA Research and SplicingFrench-language works237,207