Cancer‐associated fibroblasts‐secreted exosomal miR‐92a‐3p promotes tumor growth and stemness in hepatocellular carcinoma through activation of Wnt/β‐catenin signaling pathway by suppressing AXIN1

Abstract

AbstractCancer‐associated fibroblasts (CAFs) are a major cellular component in the tumor microenvironment and have been shown to exhibit protumorigenic effects in hepatocellular carcinoma (HCC). This study aimed to delve into the mechanisms underlying the tumor‐promoting effects of CAFs in HCC. Small RNA sequencing was conducted to screen differential expressed microRNAs in exosomes derived from CAFs and normal fibroblasts (NFs). The miR‐92a‐3p expression was then measured using reverse transcriptase quantitative real‐time PCR in CAFs, NFs, CAFs‐derived exosomes (CAFs‐Exo), and NF‐derived exosomes (NFs‐Exo). Compared to NFs or NF‐Exo, CAFs and CAFs‐Exo significantly promoted HCC cell proliferation, migration, and stemness. Additionally, compared to NFs or NF‐Exo, miR‐92a‐3p level was notably higher in CAFs and CAFs‐Exo, respectively. Exosomal miR‐92a‐3p was found to enhance HCC cell proliferation, migration, and stemness. Meanwhile, AXIN1 was targeted by miR‐92a‐3p. Exosomal miR‐92a‐3p could activate β‐catenin/CD44 signaling in HCC cells by inhibiting AXIN1 messenger RNA. Furthermore, in vivo studies verified that exosomal miR‐92a‐3p notably promoted tumor growth and stemness through targeting AXIN1/β‐catenin axis. Collectively, CAFs secreted exosomal miR‐92a‐3p was capable of promoting growth and stemness in HCC through activation of Wnt/β‐catenin signaling pathway by suppressing AXIN1. Therefore, targeting CAFs‐derived miR‐92a‐3p may be a potential strategy for treating HCC.