Editorial: Recent breakthroughs in the decoding of circulating nucleic acids and their applications to human diseases

© 2023 El-Daly, Talaat, Braoudaki, Youness and Cho. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).Peer reviewe

17β-estradiol promotes extracellular vesicle release and selective miRNA loading in ERα-positive breast cancer

The causes and consequences of abnormal biogenesis of extracellular vesicles (EVs) are not yet well understood in malignancies, including in breast cancers (BCs). Given the hormonal signaling dependence of estrogen receptor–positive (ER+) BC, we hypothesized that 17β-estradiol (estrogen) might influence EV production and microRNA (miRNA) loading. We report that physiological doses of 17β-estradiol promote EV secretion specifically from ER+ BC cells via inhibition of miR-149-5p, hindering its regulatory activity on SP1, a transcription factor that regulates the EV biogenesis factor nSMase2. Additionally, miR-149-5p downregulation promotes hnRNPA1 expression, responsible for the loading of let-7’s miRNAs into EVs. In multiple patient cohorts, we observed increased levels of let-7a-5p and let-7d-5p in EVs derived from the blood of premenopausal ER+ BC patients, and elevated EV levels in patients with high BMI, both conditions associated with higher levels of 17β-estradiol. In brief, we identified a unique estrogen-driven mechanism by which ER+ BC cells eliminate tumor suppressor miRNAs in EVs, with effects on modulating tumor-associated macrophages in the microenvironment

The Interplay between MicroRNAs and the Components of the Tumor Microenvironment in B-Cell Malignancies

An increased focus is being placed on the tumorigenesis and contexture of tumor microenvironment in hematopoietic and solid tumors. Despite recent clinical revolutions in adoptive T-cell transfer approaches and immune checkpoint blockade, tumor microenvironment is a major obstacle to tumor regression in B-cell malignancies. A transcriptional alteration of coding and non-coding RNAs, such as microRNAs (miRNAs), has been widely demonstrated in the tumor microenvironment of B-cell malignancies. MiRNAs have been associated with different clinical-biological forms of B-cell malignancies and involved in the regulation of B lymphocyte development, maturation, and function, including B-cell activation and malignant transformation. Additionally, tumor-secreted extracellular vesicles regulate recipient cell functions in the tumor microenvironment to facilitate metastasis and progression by delivering miRNA contents to neighboring cells. Herein, we focus on the interplay between miRNAs and tumor microenvironment components in the different B-cell malignancies and its impact on diagnosis, proliferation, and involvement in treatment resistance

In Vivo Genotoxicity of Gold Nanorods in Mouse Bone Marrow Compared with Cyclophosphamide

Gold nanorods (GNRs) are now under extensive investigation for biomedical applications. The in vivo genotoxic profile GNRs are not elucidated yet, therefore we investigated it in comparison with one of the most effective chemotherapeutic agents, cyclophosphamide (CP), in a mice model. PEGylated-GNRs (50 nm) were injected to Balb/C mice triple times, while CP-treated mice were treated once and the bone marrow cells (BMCs) were collected after 21 days. Chromosome aberrations, mitotic index, sister chromatid exchanges (SCEs), replicative index, micronucleus (MN) and DNA damage using comet assay were investigated. GNRs induced chromosome aberrations including- and excluding-gaps significantly at p < 0.001 and p < 0.01, respectively, however CP resulted in a higher significant increase in both types with p < 0.001. The percentage of SCEs / cell was not affected by GNRs treatment, while it was extremely significant with CP. Both mitotic activity and proliferative index were reduced dramatically with both of GNRs and CP. The recorded MN were lower in GNRs- than CP-treated mice. The percentage DNA damage, tail length and tail moment were higher in CP than GNRs. In conclusion, CP induced extreme genotoxicity more than GNRs. Both of GNRs and CP induced DNA damage. The study indicated the advantage of lower GNRs genotoxicity than that of CP. After 21 days, one injection of CP led to extreme persistent genotoxic effect more than that of multiple injections of GNRs