Extracellular vesicle‐derived circ_SLC19A1 promotes prostate cancer cell growth and invasion through the miR‐497/septin 2 pathway

Abstract

The occurrence and development of prostate cancer (PCa) is complex, and the related mechanism is not fully understood. Current studies have found that extracellular vesicles (EVs) and circular RNAs (circRNAs) have important functions in various tumours and other diseases. In this study, the detection of circRNAs in PCa showed that circ_SLC19A1 was increased in PCa cells and their secreted EVs. EVs with high expression of circ_SLC19A1 could be taken up by PCa cells, which promoted cell proliferation and invasion. The sequence of circ_SLC19A1 contained multiple binding sites for miR‐497, and circ_SLC19A1 could bind directly to miR‐497 in cells. The expression of miR‐497 was downregulated in PCa cells, while the expression of its target gene septin 2 (SEPT2) was upregulated significantly. Transfection of circ_SLC19A1 small interfering RNA (siRNA) or miR‐497 mimics could significantly inhibit the expression of SEPT2 and the phosphorylation of extracellular signal‐regulated kinase 1 and 2 (ERK1/2). After co‐transfection of circ_SLC19A1 siRNA and miR‐497 inhibitors or SEPT2 overexpression vector, the expression of SEPT2 and ERK1/2 phosphorylation levels showed no significant changes. Similar results were obtained with co‐transfection of miR‐497 mimics and the SEPT2 overexpression vector. Therefore, cancer cells can regulate the expression of SEPT2 through miR‐497 by secreting EVs with high expression of circ_SLC19A1, thus affecting the activation of the downstream ERK1/2 pathway and ultimately regulating PCa cell growth and invasion. Therefore, EV‐derived circ_SLC19A1 plays an important regulatory role in PCa and may be an important target for PCa prevention and treatment.

<p>Silencing circSLC19A1 Inhibits Prostate Cancer Cell Proliferation, Migration and Invasion Through Regulating miR-326/MAPK1 Axis</p>

“…Besides, Zheng's study showed that high circSLC19A1 expression was associated with promotion of PCa cell migration and invasion. 15 Consistent with this, we found that forced decrease of circSLC19A1 expression inhibited PCa cell proliferation, colony formation, migration and invasion, reaffirming the oncogenic role of circSLC19A1.…”

“…According to one previous study by Zheng, circSLC19A1 was highexpressed in extracellular vesicles secreted by PCa cells. 15 Similarly, we found circSLC19A1 expression was up-regulated in PCa tissues and cell lines. To further confirm the result, DU145 and PC3 cells which exhibited relatively higher circSLC19A1 expression were subjected to RNase R digestion.…”

“…Total RNA was isolated from DU145 and PC3 cells and PCa tissues using TRIzol reagent (15,596,026, ThermorFisher, USA) and total miRNA was isolated using PureLink miRNA Isolation Kits (K157001, ThermoFisher, USA). Total cytoplasmic RNA and total nuclear RNA were separately isolated using Cytoplasmic & Nuclear RNA Purification Kits (21,…”

“…To be specific, circSLC19A1 exerted promotive effects through absorbing miR-497 to upregulate septin 2 expression. 15 Thus, it is necessary for these kinds of networks that were conducive to modulating PCa progression to be uncovered. Our study tried to recognize a novel regulatory network of circSLC19A1 for PCa treatment.…”

Extracellular Vesicles as Signaling Mediators and Disease Biomarkers across Biological Barriers

“…While the mechanisms that mediate the biological effects of EVs on their cellular targets remain poorly known, it is clear that EVs are implicated in most, if not all, physiopathological processes, including signal transduction, cell growth, and differentiation, metabolic regulation, embryofetal development, organogenesis, tissue homeostasis and repair/regeneration, antigen presentation and immune response, ageing, pathogen-host interactions, carcinogenesis, tumor invasion/metastasis, cardiovascular dysfunction, etc. [9,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. The EV cargo, packaged within relatively stable membrane-bound structures, is sheltered from degradation by the extracellular enzymes present in biological fluids, and may therefore maintain biological stability over comparatively long periods of time [38].…”