Exosomal microRNAs mediating crosstalk between cancer cells and cancer-associated fibroblasts in the tumor microenvironment.

Cancer-associated fibroblasts (CAFs) play an important role in tumor formation and development by serving as the most influential stromal cells within the tumor microenvironment (TME). The communication between tumor cells and CAFs, along with the resulting impact, is more important than originally anticipated. Numerous studies have demonstrated that microRNAs (miRNAs) play an essential role in this crosstalk, and related evidence continues to emerge and advance. In addition, exosomes containing miRNAs have been found as a crucial mode of interaction between these two types of cells, with a more direct and precise role. Under the influence of exosomal miRNAs, normal fibroblasts are converted into CAFs. By doing so, CAFs can greatly promote tumor progression. Additionally, through exosomal miRNAs, activated CAFs may alter the genetic expression in tumor cells, affecting the TME and promoting malignant biological processes. Learning more about exosomal miRNAs in tumor cells and CAFs, and the intricate molecular networks that link CAFs to cancer cells, may help researchers develop more sensitive and effective cancer treatments targeting miRNAs, exosomes and CAFs, thereby giving hope to cancer patients. A comprehensive search of the literature was conducted through PubMed databases. The keywords entered for the search included: exosomes, cancer-associated fibroblasts, microRNA and cancer. This search provided information about articles published in peer-reviewed journals until 2022. Information from these articles was collected and analyzed in this review. Exosomal miRNAs can act as tumor inhibitors or tumor inducers by affecting several targets and molecular signaling pathways. MiRNAs and exosomes involved in crosstalk could have promising applications in cancer diagnosis, prognosis, and therapy. This finding about the crosstalk can help find and develop innovative miRNA-based approaches towards diagnosis, prognosis, and anti-cancer treatments.

Wang Y ，Liang H ，Zheng J 《-》

Crosstalk between Pancreatic Cancer Cells and Cancer-Associated Fibroblasts in the Tumor Microenvironment Mediated by Exosomal MicroRNAs.

Chu X ，Yang Y ，Tian X 《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

The promising role of noncoding RNAs in cancer-associated fibroblasts: an overview of current status and future perspectives.

Fang Z ，Xu J ，Zhang B ，Wang W ，Liu J ，Liang C ，Hua J ，Meng Q ，Yu X ，Shi S ... -  《Journal of Hematology & Oncology》

Cancer-associated fibroblasts promote hepatocellular carcinoma progression through downregulation of exosomal miR-150-3p.

Hepatocellular carcinoma (HCC) is a common and deadly cancer. The prognosis of HCC is poor and is related to tumor progression. The malignant potential of HCC is regulated by the tumor microenvironment (TME). As cancer-associated fibroblasts (CAFs) help regulate tumor progression, understanding how they function in HCC could improve patient outcomes. The aim of this study was to determine whether specific microRNAs (miRNAs) in exosomes derived from CAFs might be involved in HCC progression. MiRNA microarray assay was used to analyze miRNA profiles of exosomes derived from CAFs and normal fibroblasts (NFs) in HCC. Migration and invasion assays were performed to examine the effects of miR-150-3p on HCC in vitro. In addition, the relationships between prognosis of HCC patients and miR-150-3p expression in HCC tissues and plasma exosomes were retrospectively analyzed. MiR-150-3p was significantly reduced in CAFs-derived exosomes, and inhibited HCC migration and invasiveness. MiR-150-3p was transferred from CAFs transfected miR-150-3p to HCC cells through exosomes, and abrogated HCC migration and invasiveness. Furthermore, low miR-150-3p expression in HCC tissues was a significant risk factor for recurrence in HCC patients. More importantly, survival rate in patients with low miR-150-3p levels in plasma exosomes was significantly poor compared with that in patients with high miR-150-3p levels. Overall, our findings suggest that the loss of antitumoral miR-150-3p in CAFs-derived exosomes greatly promotes HCC progression. Exosomal miR-150-3p is a potential prognostic biomarker, and transferring miR-150-3p-loaded exosomes to HCC cells might become a novel therapeutic option.

Yugawa K ，Yoshizumi T ，Mano Y ，Itoh S ，Harada N ，Ikegami T ，Kohashi K ，Oda Y ，Mori M ... -  《-》

Exosomal miRNAs and miRNA dysregulation in cancer-associated fibroblasts.

Yang F ，Ning Z ，Ma L ，Liu W ，Shao C ，Shu Y ，Shen H ... -  《Molecular Cancer》