Exosomal lncRNA PVT1 promotes fibroblast activation and colon cancer progression via miR

Abstract

Colon cancer progression is closely associated with the tumor microenvironment, where cancer‐associated fibroblasts (CAFs) play a pivotal role. Exosomal long non‐coding RNAs (lncRNAs) are known to modulate the tumor stroma, but the role of lncRNA PVT1 (plasmacytoma variant translocation 1) in exosome‐mediated fibroblast activation in colon cancer remains poorly understood. This study demonstrated significantly elevated PVT1 levels in colon cancer tissues. Mechanistically, hypoxia/reoxygenation (H/R) induced the recruitment of HIF‐1α to the PVT1 promoter, directly activating its transcription and subsequent exosomal loading. Exosomes derived from H/R‐treated colon cancer cells promoted fibroblast activation into a CAF phenotype. PVT1 was found to sponge miR‐23b‐5p, thereby upregulating a network of target genes. Importantly, silencing of MAPK13 , a key downstream target, significantly abrogated the PVT1 ‐mediated fibroblast‐to‐CAF transformation. In vivo experiments confirmed that exosomal PVT1 enhanced CAF infiltration and tumor growth, whereas these effects were reversed by either restoring miR‐23b‐5p expression or knocking out PVT1 . These findings uncover a novel mechanism whereby H/R‐induced exosomal PVT1 promotes fibroblast activation and CAF transformation via the miR‐23b‐5p signaling axis, providing potential diagnostic biomarkers and therapeutic targets for modulating the tumor stroma in colon cancer. © 2026 The Pathological Society of Great Britain and Ireland.