Bystander effects can be induced through cellular communication between irradiated cells and non-irradiated cells. The signals that mediate this cellular communication, such as cytokines, reactive oxygen species, nitric oxide and even microRNAs, can be transferred between cells via gap junctions or extracellular medium. We have previously reported that miR-21, a well described DDR (DNA damage response) microRNA, is involved in radiation-induced bystander effects through a medium-mediated way. However, the mechanisms of the microRNA transfer have not been elucidated in details. In the present study, it was found that exosomes isolated from irradiated conditioned medium could induce bystander effects. Furthermore, we demonstrated plenty of evidences that miR-21, which is up-regulated as a result of mimic transfection or irradiation, can be transferred from donor or irradiated cells into extracellular medium and subsequently get access to the recipient or bystander cells through exosomes to induce bystander effects. Inhibiting the miR-21 expression in advance can offset the bystander effects to some extent. From all of these results, it can be concluded that the exosome-mediated microRNA transfer plays an important role in the radiation-induced bystander effects. These findings provide new insights into the functions of microRNAs and the cellular communication between the directly irradiated cells and the non-irradiated cells.

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Background: Accumulating literatures have indicated that long non-coding RNAs (lncRNAs) are potential biomarkers that play key roles in tumor development and progression. Urothelial cancer associated 1 (UCA1) is a novel lncRNA that acts as a potential biomarker and is involved in the development of cancers. However, the molecular mechanism of UCA1 in renal cancer is still needed to further explore. Methods: The relative expression level of UCA1 was determined by Real-Time qPCR in a total of 88 patients with urothelial renal cancer and in different renal cancer cell lines. Loss-of-function experiments were performed to investigate the biological roles of UCA1 and miR-182-5p on renal cancer cell proliferation, migration, apoptosis and tumorigenicity. Comprehensive transcriptional analysis, dual-luciferase reporter assay and western blot etc. were performed to explore the molecular mechanisms underlying the functions of UCA1. Results: In this study, we found that UCA1 was significantly up-regulated in renal cancer. Moreover, increased UCA1 expression was positively correlated with differentiation and advanced TNM stage. Further experiments demonstrated that knockdown of UCA1 inhibited malignant phenotypes and Notch signal path of renal cancer cells, and miR-182-5p was reverse function as UCA1. UCA1 functioned as a miRNA sponge to positively regulate the expression of Delta-like ligand 4(DLL4) through sponging miR-182-5p and subsequently promoted malignant phenotypes of renal cancer cells, thus UCA1 playing an oncogenic role and miR-182-5p as an antioncogenic one in renal cancer pathogenesis. Conclusion: UCA1-miR-182-5p-DLL4 axis is involved in proliferation and progression of renal cancer. Thus, this study demonstrated that UCA1 plays a critical regulatory role in renal cancer cell and UCA1 may serve as a potential diagnostic biomarker and therapeutic target of renal cancer.

Phosphorus (P), zinc (Zn), and iron (Fe) are three essential elements for plant survival, and severe deficiencies in these nutrients lead to growth retardation and crop yield reduction. This review synthesizes recent progress on how plants coordinate the acquisition and signaling of Pi, Zn, and Fe from surrounding environments and which genes are involved in these Pi–Zn–Fe interactions with the aim of better understanding of the cross-talk between these macronutrient and micronutrient homeostasis in plants. In addition, identification of genes important for interactions between Pi, Zn, and/or Fe transport and signaling is a useful target for breeders for improvement in plant nutrient acquisition. Furthermore, to understand these processes in arbuscular mycorrhizal plants, the preliminary examination of interactions between Pi, Zn, and Fe homeostasis in some relevant crop species has been performed at the physiological level and is summarized in this article. In conclusion, the development of integrative study of cross-talks between Pi, Zn, and Fe signaling pathway in mycorrhizal plants will be essential for sustainable agriculture all around the world.