Exosomal lncRNA PVT1 promotes fibroblast activation and colon cancer progression via miR-23b-5p signaling.

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.