Exosomes are a group of nano-sized membrane vesicles and are important mediators of intercellular communication, particularly in tumor microenvironment. Recently, researchers have found that circular RNAs (circRNAs), with the great research significance, are enriched and stable in exosomes. In this review, we summarize the research significance of exosomal circRNAs, sorting mechanisms and their functioning mechanisms in tumor progression. Their clinical applications as clinical tumor biomarkers and as therapeutic targets in inhibiting tumor metastasis, anti-cancer immunity response and drug resistance have been widely discussed.

BackgroundGastric cancer (GC) is one of the malignant tumors with the highest morbidity and mortality in the world. Early diagnosis combined with surgical treatment can significantly improve the prognosis of patients. Therefore, it is urgent to seek higher sensitivity and specificity biomarkers in GC. tRNA-derived small RNAs are a new non-coding small RNA that widely exists in tumor cells and body fluids. In this study, we explore the expression and biological significance of tRNA-derived small RNAs in GC.Materials and MethodsFirst of all, we screened the differentially expressed tRNA-derived small RNAs in tumor tissues by high-throughput sequencing. Agarose gel electrophoresis (AGE), Sanger sequencing, and Nuclear and Cytoplasmic RNA Separation Assay were used to screen tRF-31-U5YKFN8DYDZDD as a potential tumor biomarker for the diagnosis of GC. Then, we detected the different expressions of tRF-31-U5YKFN8DYDZDD in 24 pairs of GC and paracancerous tissues, the serum of 111 GC patients at first diagnosis, 89 normal subjects, 48 superficial gastritis patients, and 28 postoperative GC patients by quantitative real-time PCR (qRT-PCR). Finally, we used the receiver operating characteristic (ROC) curve to analyze its diagnostic efficacy.ResultsThe expression of tRF-31-U5YKFN8DYDZDD has good stability and easy detection. tRF-31-U5YKFN8DYDZDD was highly expressed in tumor tissue, serum, and cell lines of GC, and the expression was significantly related to TNM stage, depth of tumor invasion, lymph node metastasis, and vascular invasion. The expression of serum tRF-31-U5YKFN8DYDZDD in the GC patients decreased after the operation (P = 0.0003). Combined with ROC curve analysis, tRF-31-U5YKFN8DYDZDD has better detection efficiency than conventional markers.ConclusionsThe expressions of tRF-31-U5YKFN8DYDZDD in the tumor and paracancerous tissues, the serum of GC patients and healthy people, and the serum of GC patients before and after operation were different. tRF-31-U5YKFN8DYDZDD is not only a diagnostic biomarker of GC but also a predictor of poor prognosis.

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Despite the continuous improvement of various therapeutic techniques, the overall prognosis of tumors has been significantly improved, but malignant tumors in the middle and advanced stages still cannot be completely cured. It is now evident that cell adhesion-mediated resistance (CAM-DR) limits the success of cancer therapies and is a great obstacle to overcome in the clinic. The interactions between tumor cells and extracellular matrix (ECM) molecules or adjacent cells may play a significant role in initiating the intracellular signaling pathways that are associated with cell proliferation, survival upon binding to their ligands. Recent studies illustrate that these adhesion-related factors may contribute to the survival of cancer cells after chemotherapeutic therapy, advantageous to resistant cells to proliferate and develop multiple mechanisms of drug resistance. In this review, we focus on the molecular basis of these interactions and the main signal transduction pathways that are involved in the enhancement of the cancer cells’ survival. Furthermore, therapies targeting interactions between cancer cells and their environment to enhance drug response or prevent the emergence of drug resistance will also be discussed.