The promising role of noncoding RNAs in cancer-associated fibroblasts: an overview of current status and future perspect
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The promising role of noncoding RNAs in cancer‑associated fibroblasts: an overview of current status and future perspectives Zengli Fang1,2,3,4†, Jin Xu1,2,3,4†, Bo Zhang1,2,3,4†, Wei Wang1,2,3,4, Jiang Liu1,2,3,4, Chen Liang1,2,3,4, Jie Hua1,2,3,4, Qingcai Meng1,2,3,4*, Xianjun Yu1,2,3,4* and Si Shi1,2,3,4*
Abstract As the most important component of the stromal cell population in the tumor microenvironment (TME), cancerassociated fibroblasts (CAFs) are crucial players in tumor initiation and progression. The interaction between CAFs and tumor cells, as well as the resulting effect, is much greater than initially expected. Numerous studies have shown that noncoding RNAs (ncRNAs) play an irreplaceable role in this interplay, and related evidence continues to emerge and advance. Under the action of ncRNAs, normal fibroblasts are directly or indirectly activated into CAFs, and their metabolic characteristics are changed; thus, CAFs can more effectively promote tumor progression. Moreover, via ncRNAs, activated CAFs can affect the gene expression and secretory characteristics of cells, alter the TME and enhance malignant biological processes in tumor cells to contribute to tumor promotion. Previously, ncRNA dysregulation was considered the main mechanism by which ncRNAs participate in the crosstalk between CAFs and tumor cells. Recently, however, exosomes containing ncRNAs have been identified as another vital mode of interaction between these two types of cells, with a more direct and clear function. Gaining an in-depth understanding of ncRNAs in CAFs and the complex regulatory network connecting CAFs with tumor cells might help us to establish more effective and safer approaches for cancer therapies targeting ncRNAs and CAFs and offer new hope for cancer patients. Keywords: Noncoding RNA, MicroRNA, Long noncoding RNA, Cancer-associated fibroblasts, Tumor microenvironment, Cancer, Exosome, Cell–cell interaction Introduction Tumor progression is not an independent event related only to the biological characteristics of tumor cells but instead is a process affected and modulated by many factors. One of these factors, the tumor microenvironment (TME), is vital for tumor initiation, progression, metastasis, immunosuppression and therapeutic resistance [1, 2]. The TME consists of cancer-associated fibroblasts *Correspondence: [email protected]; [email protected]; [email protected] † Zengli Fang, Jin Xu, and Bo Zhang contributed equally to this work. 1 Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 Dong’An Road, Shanghai 200032, China Full list of author information is available at the end of the article
(CAFs), macrophages, myeloid-derived suppressor cells (MDSCs), lymphocytes, antigen-presenting cells and other tumor-associated stromal cells, as well as microvessels, lymphatic vessels, nerves, infiltrating biomolecules and extracellular matrix (ECM) components [3, 4]. As the key components among these constituents, CAFs are abundant in the TME (espe
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