LINC02888 promotes HGSOC progression and immune evasion via PPIB-mediated stabilization of LAPTM5 mRNA and inhibition of RIG-I-like receptor signaling
Bibliographic record
Abstract
BACKGROUND: High-grade serous ovarian cancer (HGSOC) remains highly lethal due to late diagnosis and chemoresistance. Long noncoding RNAs (lncRNAs) have emerged as critical regulators of tumor progression. This study investigates the role of the cytoplasmic lncRNA LINC02888 in HGSOC. METHODS: We identified overexpression of LINC02888 in HGSOC tissues and cell lines through whole-transcriptome sequencing, qPCR, in situ hybridization, and analyses of TCGA/GTEx datasets. Functional assays including CCK-8, EdU, colony formation, wound healing, Transwell migration/invasion, and flow cytometry were performed after modulating LINC02888 expression. RNA pull-down coupled with mass spectrometry identified the RNA-binding protein PPIB as an interactor of LINC02888. RNA-seq following both LINC02888 and PPIB knockdown, along with Western blot, qPCR analyses and functional assays, revealed that LAPTM5 is a downstream effector. Furthermore, RIP-qPCR, deletion mapping, and ActD assays confirmed that LINC02888 binds PPIB, which stabilizes LAPTM5 mRNA via its 3'UTR. The effect on the RIG-I-like receptor pathway was evaluated by measuring the expression levels of RIG-I, IRF7, and ISG15. Finally, in vivo, the critical role of the LINC02888/PPIB/ LAPTM5 axis in ovarian tumor progression were explored by axillary subcutaneous injection of specifically transfected OVCAR3 cells into nude mice. RESULTS: LINC02888 was significantly upregulated in HGSOC tissues and correlated with advanced disease and poor prognosis. Silencing LINC02888 inhibited proliferation, migration, and invasion, while inducing apoptosis; conversely, overexpression promoted these oncogenic behaviors. Mechanistically, LINC02888 interacts with PPIB to stabilize LAPTM5 mRNA via its 3'UTR, resulting in elevated LAPTM5 protein levels and suppression of RIG-I-like receptor signaling. Rescue experiments confirmed the critical role of the LINC02888-PPIB-LAPTM5 axis in HGSOC progression in vivo and vitro. CONCLUSIONS: Our findings reveal that LINC02888 drives HGSOC progression through a mechanism involving PPIB-mediated stabilization of LAPTM5 mRNA, which suppresses RIG-I-like receptor signaling. It also appropriately suggests that inhibiting this innate immune pathway may contribute to an immunosuppressive tumor microenvironment, making the LINC02888-PPIB-LAPTM5 axis a promising therapeutic target for this aggressive malignancy.
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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 | 0.001 | 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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".