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.

Autor: Su Z; Department of Oncology, Inner Mongolia People's Hospital, People's Hospital of Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, China.; Institute of Cancer, Inner Mongolia People's Hospital, People's Hospital of Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, China.; Department of Graduate School, Baotou Medical College, Baotou, Inner Mongolia Autonomous Region, China., Lu C; Department of Oncology, Inner Mongolia People's Hospital, People's Hospital of Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, China.; Institute of Cancer, Inner Mongolia People's Hospital, People's Hospital of Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, China.; Department of Graduate School, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China., Zhang F; Department of Nuclear Medicine, Inner Mongolia People's Hospital, People's Hospital of Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, China., Liu H; Department of Oncology, Inner Mongolia People's Hospital, People's Hospital of Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, China.; Institute of Cancer, Inner Mongolia People's Hospital, People's Hospital of Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, China.; Department of Graduate School, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China., Li M; Department of Oncology, Inner Mongolia People's Hospital, People's Hospital of Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, China.; Institute of Cancer, Inner Mongolia People's Hospital, People's Hospital of Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, China., Qiao M; Department of Oncology, Inner Mongolia People's Hospital, People's Hospital of Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, China.; Institute of Cancer, Inner Mongolia People's Hospital, People's Hospital of Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, China., Zou X; Department of Oncology, Inner Mongolia People's Hospital, People's Hospital of Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, China.; Institute of Cancer, Inner Mongolia People's Hospital, People's Hospital of Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, China., Luo D; Department of Oncology, Inner Mongolia People's Hospital, People's Hospital of Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, China.; Institute of Cancer, Inner Mongolia People's Hospital, People's Hospital of Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, China., Li H; Department of Oncology, Inner Mongolia People's Hospital, People's Hospital of Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, China.; Institute of Cancer, Inner Mongolia People's Hospital, People's Hospital of Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, China., He M; Department of Oncology, Inner Mongolia People's Hospital, People's Hospital of Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, China.; Institute of Cancer, Inner Mongolia People's Hospital, People's Hospital of Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, China., Se H; Department of Graduate School, Baotou Medical College, Baotou, Inner Mongolia Autonomous Region, China., Jing J; Department of Graduate School, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China., Wang X; Department of Nuclear Medicine, Shenzhen People's Hospital, Shenzhen, Guangzhou, China., Yang H; Department of Radiation Oncology, Peking University Cancer Hospital (Inner Mongolia Campus) & Affiliated Cancer Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China., Yang H; Department of Oncology, Inner Mongolia People's Hospital, People's Hospital of Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, China.; Institute of Cancer, Inner Mongolia People's Hospital, People's Hospital of Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, China.
Jazyk: angličtina
Zdroj: Journal of cellular physiology [J Cell Physiol] 2024 Sep; Vol. 239 (9), pp. e31344. Date of Electronic Publication: 2024 Jul 01.
DOI: 10.1002/jcp.31344
Abstrakt: Cancer-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.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
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