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Record W7132861899

Investigating WDR12 as a Therapeutic Target in Breast Cancer

2023· dissertation· W7132861899 on OpenAlexfundno aff
Ji Sup Kim

Bibliographic record

VenueTSpace · 2023
Typedissertation
Language
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA and protein synthesis mechanisms
Canadian institutionsnot available
FundersUniversity of Toronto
KeywordsGene knockdownBreast cancerRibosome biogenesisCell growthEndoplasmic reticulumCancerRibosomeCancer cell
DOInot available

Abstract

fetched live from OpenAlex

Breast cancer is the most diagnosed and lethal cancer globally in women. Presently, there is a need for novel targets for the development of improved therapeutics. Data mining through genetic screens suggests that the ribosome biogenesis protein WDR12 is essential for breast cancer cell proliferation. In this study, we characterize the effects of WDR12 knockdown in a panel of breast cancer cells. We show that WDR12 knockdown induces ribosomal RNA (rRNA) processing defects resulting in strong growth inhibition in all breast cancer cells tested, however only a subset of lines displayed short-term cell cycle defects. To further understand the cellular consequences of WDR12 suppression, we investigated the global proteomic landscape and found that WDR12 knockdown results in a perturbation of translational and ribosome biogenesis-related networks. Furthermore, we performed RNA-sequencing to assess the global transcriptional changes upon WDR12 knockdown and found dysregulation of the endoplasmic reticulum (ER) stress response pathway. Finally, we characterized the effect of long-term WDR12 suppression and found that growth inhibition was in part due to cellular senescence. Our results demonstrate that WDR12 is implicated in breast cancer cell growth and senescence, and its suppression may represent a viable therapeutic target for breast cancer.

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.001

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 head0.020
GPT teacher head0.331
Teacher spread0.311 · 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 source (direct Gemma or distilled Codex), 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

Citations0
Published2023
Admission routes1
Has abstractyes

Explore more

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