The crosstalk between circular RNAs and the tumor microenvironment in cancer metastasis
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ancer Cell International Open Access
REVIEW
The crosstalk between circular RNAs and the tumor microenvironment in cancer metastasis Ying Shao and Bingjian Lu*
Abstract Background: Carcinomas are highly heterogeneous with regard to various cancer cells within a tumor microenvironment (TME), which is composed of stromal cells, blood vessels, immunocytes, and modified extracellular matrix. Focus of the study: Circular RNAs (circRNAs) are non-coding RNAs that are expressed in cancer and stromal cells. They are closely associated with cancer metastasis as their expression in tumor cells directs the latter to migrate to different organs. circRNAs packaged in exosomes might be involved in this process. This is particularly important as the TME acts in tandem with cancer cells to enhance their proliferation and metastatic capability. In this review, we focus on recent studies on the crosstalk between circRNAs and the TME during cancer metastasis. Conclusion: We particularly emphasize the roles of the interaction between circRNAs and the TME in anoikis resistance, vessel co-option, and local circRNA expression in directing homing of exosome. Keywords: Metastasis, Circular RNA, Tumor microenvironment, Invasion, Cancer Background The “seed-soil” description proposed by Stephen Paget in 1889 [1] is the classical theory of cancer metastasis. Cancer cells move from the primary neoplasm to a target distant location. The host environment, described as the “soil”, is remodeled to facilitate tumor metastasis, and the “seed” represents the cancer cells colonizing a new site suitable for tumor growth and progression. The cancer invasion-metastasis cascade consists of a series of discrete biological processes. Initially, cancer cells invade the surrounding tissue and enter the circulation, followed by their extravasation into a new site where they evade immune surveillance and anoikis to develop into metastatic tumors [2]. Various studies have considered the influence of the tumor microenvironment (TME) on cancer metastasis. The TME is composed of stromal *Correspondence: [email protected] Department of Surgical Pathology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
cells, immune cells, vasculature, and extracellular matrix (ECM) [3]. Pervasive stromal reprogramming and ECM remodeling in the TME play vital roles in cancer metastasis [4]. Circular RNAs (circRNAs) are a novel type of noncoding RNAs that form covalently closed loop structures without 5′-caps or 3′-polyadenylated tails. They are ubiquitous and play critical roles in carcinogenesis. Cumulative evidence has shown that circRNAs are closely associated with cancer metastasis [5–7]. The interaction between circRNAs and the TME has significant clinical relevance to cancer therapy [8, 9]. Therefore, in the current review, we focus on the crosstalk between circRNAs and the TME in cancer metastasis.
Biogenesis and functions of circRNAs CircRNAs are produced by back splicing, which is different from the classical splicing of linear RNAs.
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