Endothelial progenitor cells (EPCs), which are a type of stem cell, have been found to have strong angiogenic and tissue repair capabilities. Extracellular vesicles (EVs) contain many effective components, such as cellular proteins, microRNAs, messenger RNAs, and long noncoding RNAs, and can be secreted by different cell types. The functions of EVs depend mainly on their parent cells. Many researchers have conducted functional studies of EPC-derived EVs (EPC-EVs) and showed that they exhibit therapeutic effects on many diseases, such as cardiovascular disease, acute kidney injury, acute lung injury, and sepsis. In this review article, we comprehensively summarized the biogenesis and functions of EPCs and EVs and the potent role of EPC-EVs in the treatment of various diseases. Furthermore, the current problems and future prospects have been discussed, and further studies are needed to compare the therapeutic effects of EVs derived from various stem cells, which will contribute to the accelerated translation of these applications in a clinical setting.
Renal cell carcinoma (RCC) originates from the epithelial cells of the renal tubules and has a high degree of malignancy and heterogeneity. Recent studies have found that exosomes regulate intercellular communication via transferring various bioactive molecules, such as circular RNAs (circRNAs), which are critical for cancer progression. However, the role of tumor cell-derived exosomal circRNAs in RCC remains unclear. In this study, we reported the high expression of circ-PRKCI in RCC tissues and serum exosomes. We also found that circ-PRKCI could be transferred exosomally from highly malignant RCC cells to relatively less malignant RCC cells. Tumor cell-derived exosomal circ-PRKCI promoted the proliferation, migration, and invasion of RCC cells, while inhibiting their apoptosis. Mechanistically, we found that circ-PRKCI promoted the proliferation of RCC via the miR-545-3p/CCND1 signaling pathway. Our study is the first to report the potential mechanisms of tumor cell-derived exosomal circ-PRKCI in RCC. In conclusion, this study will provide a new understanding about the molecular mechanisms of RCC progression.
Background: Polo-like kinase 1 (PLK1) belongs to polo-like kinases family and affects cell cycles. However, the role of PLK1 in some malignant tumors remains unclear. Methods: To obtain a comprehensive view of PLK1 expression patterns, public databases including The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, the Genotype-Tissue Expression, and human cell landscape databases were employed. The correlation of PLK1 expression with prognosis, immune infiltrations, immune checkpoint genes, tumor mutational burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), and DNA methylation was examined. Besides, we validated the results of clear cell renal cell carcinoma (ccRCC) in two cohorts, with quantitative real-time PCR, Western blot, and loss-of-function experiments. Results: By mining public datasets, we discovered that PLK1 expression in tumor tissues and cancer cell lines displayed heterogeneity compared to normal controls across different cancers. Besides, high expression of PLK1 results in shorter survival time in 15 cancer types, especially in ccRCC. PLK1 expression showed strong association with immune cell infiltration and immune checkpoint genes across cancer types. Moreover, we identified a strong association between PLK1 expression and TMB, MSI MMR, and DNA methylation. PLK1 was validated to be highly expressed in ccRCC tissues and promote ccRCC cell proliferation, migration, invasion, and cell cycle. Mechanistically, PLK1 could regulate forkhead box protein M1 and target cell cycle-associated genes to participate in cell cycle control. Conclusion: PLK1 has important prognostic value and is associated with tumor immunity across cancer types including ccRCC.
Circular RNAs (circRNAs) are a novel group of endogenous RNAs with a circular structure. Growing evidence indicates that circRNAs are involved in a variety of human diseases including malignancies. CircRNA ZNF609 (circ‐ZNF609), derived from the ZNF609 gene sequence, has been demonstrated to be involved in the development and progression of many diseases. circ‐ZNF609 is thought to be a viable diagnostic and prognostic biomarker for several diseases and might be a new therapeutic target, but further research is needed to accelerate clinical application. Here, we review the biogenesis and function of circRNAs and the functional roles and molecular mechanism related to circ‐ZNF609 in neoplasms and other diseases.
Background: Prolyl 4-hydroxylase subunit alpha 1 (P4HA1) provides the majority of the catalytic site of the active P4H enzyme. Emerging evidence has revealed that P4HA1 participates in the initiation and development of several malignant tumors. However, a pan-cancer analysis of P4HA1 has not been performed.Methods: In this study, we carried out an in-depth analysis of the expression patterns and prognostic value of P4HA1 using the datasets of The Cancer Genome Atlas (TCGA) and Kaplan–Meier Plotter. Genomic and epigenetic alterations of P4HA1 and the correlation of P4HA1 with DNA methylation in different cancers were also analyzed across multiple databases. In addition, the purity-adjusted partial Spearman’s correlation test was utilized to evaluate the correlation between P4HA1 expression and immune cell infiltration. We also further explored the biological function and mechanism of P4HA1 in renal cell carcinoma (RCC).Results: We characterized the expression profiles and prognostic values of P4HA1 in multiple cancer types. P4HA1 expression was increased in clear cell renal cell carcinoma (RCC) compared to adjacent normal tissues, and P4HA1 positively correlated with the overall survival (OS) and disease-free survival (DFS) in papillary RCC. In addition, a positive correlation between P4HA1 expression and immune cell infiltration was observed in clear cell RCC. We also identified a strong correlation between P4HA1 expression and immune checkpoint gene expression, microsatellite instability, and tumor mutation burden in chromophobe RCC. Finally, the results of in vitro experiments verified that overexpression of P4HA1 promoted the proliferation, migration, invasion, and epithelial–mesenchymal transition of RCC cells.Conclusion: Overall, our study has suggested that P4HA1 might play a significant role in tumorigenesis in RCC and may be a prognostic biomarker and therapeutic target for several malignant tumors, including RCC.
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