1.
Cross-kingdom regulation by dietary plant miRNAs: an evidence-based review with recent updates.
Jia, M, He, J, Bai, W, Lin, Q, Deng, J, Li, W, Bai, J, Fu, D, Ma, Y, Ren, J, et al
Food & function. 2021;(20):9549-9562
Abstract
As non-coding RNA molecules, microRNAs (miRNAs) are widely known for their critical role in gene regulation. Recent studies have shown that plant miRNAs obtained through dietary oral administration can survive in the gastrointestinal (GI) tract, enter the circulatory system and regulate endogenous mRNAs. Diet-derived plant miRNAs have 2'-O-methylated modified 3'ends and high cytosine and guanine (GC) content, as well as exosomal packaging, which gives them high stability even in the harsh environment of the digestive system and circulatory system. The latest evidence shows that dietary plant miRNAs can not only be absorbed in the intestine, but also be absorbed and packaged by gastric epithelial cells and then secreted into the circulatory system. Alternatively, these biologically active plant-derived miRNAs may also affect the health of the host by affecting the function of the microbiome, while not need to be taken into the host's circulatory system and transferred to remote tissues. This cross-kingdom regulation of miRNAs gives us hope for exploring their therapeutic potential and as dietary supplements. However, doubts have also been raised about the cross-border regulation of miRNAs, suggesting that technical flaws in the experiments may have led to this hypothesis. In this article, we summarize the visibility of dietary plant miRNAs in the development of human health and recent research data on their use in therapeutics. The regulation of plant miRNAs across kingdoms is a novel concept. Continued efforts in this area will broaden our understanding of the biological role of plant miRNAs and will open the way for the development of new approaches to prevent or treat human diseases.
2.
Elevating microRNA-1-3p shuttled by cancer-associated fibroblasts-derived extracellular vesicles suppresses breast cancer progression and metastasis by inhibiting GLIS1.
Tao, S, Li, H, Ma, X, Ma, Y, He, J, Gao, Y, Li, J
Cancer gene therapy. 2021;(6):634-648
Abstract
Cancer-associated fibroblasts (CAFs) play supporting roles in tumor progression by releasing microvesicles that transmit oncogenic cargoes. Indeed, extracellular vesicles (EVs) have emerged as important vehicles to deliver proteins, messenger RNAs (mRNAs), and microRNAs (miRs) between cells. In this study, we aimed to outline the role and function of CAFs-derived EVs carrying miR-1-3p in breast cancer. We first experimentally determined downregulated miR-1-3p in breast cancer tissues. EVs were isolated from CAFs extracted from breast cancer tissues, which showed downregulated miR-1-3p expression relative to EVs derived from normal fibroblasts (NFs). In a co-culture system, miR-1-3p cargo was transported into breast cancer cells via CAF-derived EVs. In gain-of-function experiments, the elevation of miR-1-3p in breast cancer cells inhibited cell viability, invasion, migration, and epithelial-to-mesenchymal transition, and suppressed tumor formation and metastasis. Furthermore, EVs derived from CAFs transfected with miR-1-3p mimic were more effective in transferring miR-1-3p to suppress cancer progression and metastasis. Krüppel-like zinc-finger protein Gli-similar 1 (GLIS1) was predicted to be a putative target of miR-1-3p, which was subsequently confirmed by dual-luciferase reporter assay. We then demonstrated that overexpression of GLIS1 neutralized the effects of miR-1-3 on the development of breast cancer in vitro. These findings shed light on the underlying mechanism by which CAFs-derived EVs carrying miR-1-3p mediate the progression and metastasis of breast cancer, and highlight the potential of miR-1-3p shuttled by CAFs-derived EVs serving as a therapeutic target for breast cancer.