Long non-coding RNA LINC00649 regulates YES-associated protein 1 (YAP1)/Hippo pathway to accelerate gastric cancer (GC) progression via sequestering miR-16-5p
Bibliographic record
Abstract
Although long non-coding RNA (LncRNA) LINC00649 is reported to be closely associated with acute myeloid leukemia (AML), prostate cancer and colorectal cancer, its role in regulating other types of cancer, such as gastric cancer (GC), has not been studied. This study analyzed the expression status of LINC00649 in GC tissues and cells by performing Real-Time qPCR analysis, and we found that LINC00649 tended to be enriched in cancerous tissues and cells but not in their normal counterparts, which were supported by the data from TCGA dataset. Next, by performing the gain- and loss-of-function experiments, we expectedly found that LINC00649 acted as an oncogene to accelerate GC cell proliferation, migration and epithelial-mesenchymal transition (EMT) <i>in vitro</i> and promote its tumorigenesis <i>in vivo</i>. Moreover, the online miRDB software predicted that miR-16-5p bound to both LINC00649 and 3ʹ untranslated region (3ʹUTR) of YAP1 mRNA, which were validated by the following dual-luciferase reporter gene system assay and RNA pull-down assay. Finally, we proved that LINC00649 exerted its tumor-promoting effects in GC by regulating the miR-16-5p/YES-associated protein 1 (YAP1)/Hippo pathway. Mechanistically, knock-down of LINC00649 suppressed YAP1 expressions by releasing miR-16-5p, resulting in the recovery of the Hippo pathway, which suppressed the expression levels of the downstream oncogenes, including EGFR, SOX2 and OCT4, leading to the inhibition of the malignant phenotypes in GC cells. In conclusion, this study, for the first time, evidenced that LINC00649 promoted GC progression by targeting the miR-16-5p/YAP1/Hippo signaling pathway, which provided potential diagnostic and therapeutic indicators for GC treatment for clinical utilization.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.017 | 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".