ABHD11-AS1 Suppresses Colorectal Cancer Progression by Disrupting EIF4E-mediated POU2F1 Ubiquitination.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, yet the underlying mechanisms driving its progression are not fully elucidated. Long non-coding RNAs (lncRNAs) have recently emerged as key regulatory molecules in tumor biology. In this study, we identified ABHD11-AS1 as a tumor-suppressive lncRNA that is significantly downregulated in CRC tissues, its low expression is correlated with poor patient prognosis. Functional assays demonstrated that ABHD11-AS1 inhibits CRC cell proliferation, migration, and invasion, and enhances sensitivity to oxaliplatin. Mechanistically, ABHD11-AS1 directly binds to EIF4E and disrupts its phase separation, thereby suppressing the translation of USP18, a deubiquitinating enzyme that stabilises the oncogenic protein POU2F1. Reduced USP18 expression leads to increased ubiquitination and proteasomal degradation of POU2F1, ultimately inhibiting malignant progression and enhancing chemotherapy sensitivity. Collectively, our findings uncover a previously unrecognised mechanism by which ABHD11-AS1 modulates EIF4E-mediated phase separation to regulate protein homeostasis, highlighting its potential as a therapeutic target in CRC.