Effects of CAF-Derived MicroRNA on Tumor Biology and Clinical Applications

SIMPLE SUMMARY: Cancer-associated fibroblasts (CAFs), as an important part of the tumor environment (TME), facilitate the progression of tumorigenesis, the development of metastasis, and chemoresistance. MiRNAs—one of the media through which CAFs function—are actively secreted into the TME within exosomes and taken up by specific target cells. Aberrantly expressed miRNAs exert tumor-suppressive or oncogenic functions through negatively regulating gene expression by post-transcription modification. In this review, we describe miRNAs that are differentially expressed by NFs and CAFs, summarize the modulating role of CAF-derived miRNAs in fibroblast activation and tumor advance, and, eventually, identify a potential clinical application for CAF-derived miRNAs as diagnostic/prognostic biomarkers and therapeutic targets in several tumors. ABSTRACT: Cancer-associated fibroblasts (CAFs), prominent cell components of the tumor microenvironment (TME) in most types of solid tumor, play an essential role in tumor cell growth, proliferation, invasion, migration, and chemoresistance. MicroRNAs (miRNAs) are small, non-coding, single-strand RNAs that negatively regulate gene expression by post-transcription modification. Increasing evidence has suggested the dysregulation of miRNAs in CAFs, which facilitates the conversion of normal fibroblasts (NFs) into CAFs, then enhances the tumor-promoting capacity of CAFs. To understand the process of tumor progression, as well as the development of chemoresistance, it is important to explore the regulatory function of CAF-derived miRNAs and the associated molecular mechanisms, which may become potential diagnostic and prognostic biomarkers and targets of anti-tumor therapeutics. In this review, we describe miRNAs that are differentially expressed by NFs and CAFs, summarize the modulating role of CAF-derived miRNAs in fibroblast activation and tumor advance, and eventually identify a potential clinical application for CAF-derived miRNAs as diagnostic/prognostic biomarkers and therapeutic targets in several tumors.