Pan-gastrointestinal prioritization links LINC01094 to a colorectal cancer transcriptional state and replication-associated checkpoint activation
- 1Rosalind Franklin University of Medicine and Science
Abstract
Cancer transcriptomes nominate many disease-associated long noncoding RNAs (lncRNAs), but functional prioritization remains difficult. Here, we integrated recurrent tumor upregulation, clinical association, co-expression network context, and malignant epithelial detectability across colorectal, gastric, and esophageal cancers, identifying five lncRNAs with convergent clinical and network support. We selected the intergenic lncRNA LINC01094 for functional characterization in colorectal cancer (CRC). Across 52 CRC cell lines, endogenous LINC01094 expression defined a transcriptional state linking higher expression to extracellular matrix, adhesion, and inflammatory programs and lower expression to DNA replication, mitochondrial, and ribosome/RNP programs. Acute CRISPR interference (CRISPRi)-mediated depletion in HCT116 cells produced a nearly inverse transcriptional response; among 764 GO terms significant in both analyses, 748 (97.9%) changed in opposite directions (Pearson r = -0.962). Functionally, LINC01094 depletion impaired cell growth in both HCT116 and Caco-2 cells. In HCT116 cells, depletion reduced DNA synthesis despite induction of replication-associated transcriptional programs and was accompanied by increased {gamma}H2AX, CHK1 Ser345 phosphorylation, and p21 accumulation without detectable apoptotic execution. {gamma}H2AX foci were also elevated within residual EdU-positive nuclei. The predominant LINC01094 transcript in HCT116 cells was nuclear-enriched, whereas SLPI, a reported effector of a cytoplasmic miR-1266-5p/SLPI ceRNA model in CRC, was not reproducibly altered following LINC01094 depletion in either CRC model. These findings link LINC01094 to maintenance of a CRC-associated transcriptional state and show that its acute disruption is accompanied by impaired productive DNA synthesis, replication-associated DNA-damage signaling, and checkpoint activation, supporting a broader, context-dependent role for LINC01094 beyond previously described pathway-specific models.
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BibTeX
@misc{flowers2026pangastrointestinal,
title = {{Pan-gastrointestinal prioritization links LINC01094 to a colorectal cancer transcriptional state and replication-associated checkpoint activation}},
author = {B. Flowers and P. Lialios and E. Park and N. Smith and R. J. Burgess and J. Whalley and J.-S. Lee},
howpublished = {bioRxiv},
year = {2026},
month = may,
doi = {10.64898/2026.05.26.728026},
url = {https://www.biorxiv.org/content/10.64898/2026.05.26.728026v2},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Pan-gastrointestinal prioritization links LINC01094 to a colorectal cancer transcriptional state and replication-associated checkpoint activation
AU - B. Flowers
AU - P. Lialios
AU - E. Park
AU - N. Smith
AU - R. J. Burgess
AU - J. Whalley
AU - J.-S. Lee
PY - 2026
DA - 2026/05/26
PB - bioRxiv
DO - 10.64898/2026.05.26.728026
UR - https://www.biorxiv.org/content/10.64898/2026.05.26.728026v2
AB - Cancer transcriptomes nominate many disease-associated long noncoding RNAs (lncRNAs), but functional prioritization remains difficult. Here, we integrated recurrent tumor upregulation, clinical association, co-expression network context, and malignant epithelial detectability across colorectal, gastric, and esophageal cancers, identifying five lncRNAs with convergent clinical and network support. We selected the intergenic lncRNA LINC01094 for functional characterization in colorectal cancer (CRC). Across 52 CRC cell lines, endogenous LINC01094 expression defined a transcriptional state linking higher expression to extracellular matrix, adhesion, and inflammatory programs and lower expression to DNA replication, mitochondrial, and ribosome/RNP programs. Acute CRISPR interference (CRISPRi)-mediated depletion in HCT116 cells produced a nearly inverse transcriptional response; among 764 GO terms significant in both analyses, 748 (97.9%) changed in opposite directions (Pearson r = -0.962). Functionally, LINC01094 depletion impaired cell growth in both HCT116 and Caco-2 cells. In HCT116 cells, depletion reduced DNA synthesis despite induction of replication-associated transcriptional programs and was accompanied by increased {gamma}H2AX, CHK1 Ser345 phosphorylation, and p21 accumulation without detectable apoptotic execution. {gamma}H2AX foci were also elevated within residual EdU-positive nuclei. The predominant LINC01094 transcript in HCT116 cells was nuclear-enriched, whereas SLPI, a reported effector of a cytoplasmic miR-1266-5p/SLPI ceRNA model in CRC, was not reproducibly altered following LINC01094 depletion in either CRC model. These findings link LINC01094 to maintenance of a CRC-associated transcriptional state and show that its acute disruption is accompanied by impaired productive DNA synthesis, replication-associated DNA-damage signaling, and checkpoint activation, supporting a broader, context-dependent role for LINC01094 beyond previously described pathway-specific models.
ER -