Pan-gastrointestinal prioritization links LINC01094 to a colorectal cancer transcriptional state and replication-associated checkpoint activation

Acute CRISPRi depletion of LINC01094 in colorectal cancer cells impairs productive DNA synthesis and triggers replication-associated DNA-damage signaling, including increased γH2AX and CHK1 Ser345 phosphorylation.

• Why it matters: Functional prioritization of cancer-associated lncRNAs is difficult because transcriptome signals rarely indicate which lncRNAs control malignant transcriptional states and replication-linked checkpoint responses.
• What they did: Using pan-gastrointestinal integration, the study prioritized LINC01094, then profiled 52 CRC cell lines and performed CRISPRi in HCT116 and Caco-2, including GO-term overlap (748/764; 97.9%) and DNA-damage markers.
• The result: In HCT116, LINC01094 depletion reduced DNA synthesis while inducing replication-associated transcriptional programs, increased γH2AX foci in residual EdU-positive nuclei, elevated p21, and activated checkpoint signaling without detectable apoptotic execution.