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Preprint WatchModerateSeptember 9th, 2026

CAMOR and specific oncogene-driven lncRNAs mediate carcinogenic functions downstream of MYC, mutant KRAS, and mutant TP53

Grzes, M.; Jaiswar, A.; Kazmierczak, W.; Olesinski, T.; Nowak-Niezgoda, M.; Walerych, D.

Identifies RAKRAR as a KRAS-dependent long non-coding RNA and CAMOR as a pan-driver lncRNA upregulated by MYC, mutant KRAS and mutant TP53, each promoting cancer cell viability, migration and clonogenicity downstream of the oncogenic driver.

Moderate contradiction

2 prior failures

Two documented clinical failures match this mechanism, or a single Phase 3 failure is on record.

This preprint places new carcinogenic effectors downstream of mutant KRAS rather than at the mutant protein itself, which is where the Claidex record on this target sits. Two documented KRAS failures are on file and neither turned on the biology being proposed here. bgb-53038-kras-solid-tumors-phase1-strategic-reprioritization ended as a portfolio decision in Phase 1, and sotorasib-durvalumab-kras-g12c-ctdna-stage3-nsclc-phase2-enrollment-collapse ended on accrual rather than on a read of KRAS pharmacology. The relevant caution is therefore not that direct KRAS inhibition has been falsified, because it has not been in this record, but that a downstream lncRNA effector adds a further layer of tissue-context dependence to a target whose recent clinical setbacks were operational and strategic. A programme building on CAMOR or RAKRAR should state which tumour context it expects the effector to be load-bearing in, and how that context maps onto a trial population that can actually be enrolled.

Abstract excerpt

Purpose Long non-coding RNAs (lncRNAs) are important regulators of tumor biology, but their dependence on major oncogenic drivers and cancer specificity remain poorly characterized. We aimed to identify lncRNAs regulated by MYC, mutant KRAS, and mutant TP53 across colorectal, lung, and pancreatic cancer and to determine their functional relevance and molecular mechanism. Methods We performed an integrative analysis of lncRNA expression profiles driven by MYC, mutant KRAS, and mutant TP53 across colorectal, lung, and pancreatic cancer cell lines. Candidate lncRNAs were functionally characterized using assays of cancer cell viability, migration, and clonogenicity. Expression in patient-derived tumor and normal tissues and downstream molecular pathways were investigated. Results MYC was associated with the most extensive lncRNA regulation, with expression patterns largely independent of tissue origin. MYC-dependent LINC00997 and the previously uncharacterized AC104447.1, as well as specifically KRAS-dependent RAKRAR (RASSF3 antisense KRAS regulated lncRNA) promoted cancer cell viability, migration, and clonogenicity. LINC00997 and AC104447.1 expression was elevated in specific tumor types compared to normal tissues. We identified CAMOR (CARNMT1 Antisense Multiple-Oncoprotein Regulated lncRNA), a pan-cancer lncRNA upregulated by all three oncogenic drivers. CAMOR promoted viability and migration specifically in cancer cells across analyzed cell lines and tumor types. Mechanistically, CAMOR and neighboring CARNMT1 form a negative feedback regulatory loop affecting CAMOR oncogenic activity. Distinct downstream gene expression signatures suggested that the studied lncRNAs act through different regulatory processes. Conclusion Our findings expand the repertoire of oncogenic lncRNAs and demonstrate that integrating multiple oncogenic contexts enables identification of both driver-specific and broadly acting lncRNAs, providing a framework for identifying lncRNAs that may contribute to cancer development and represent potential diagnostic or therapeutic targets.

Matching Claidex post-mortems

2 of 2 indexed

This is an automated contradiction flag, not an editorial judgment on the preprint's quality. Flags identify where the preclinical literature and the clinical failure record diverge.