SummaryGround-state pluripotency is a cell state in which pluripotency is established and maintained through efficient repression of endogenous differentiation pathways. Self-renewal and pluripotency of embryonic stem cells (ESCs) are influenced by ESC-associated microRNAs (miRNAs). Here, we provide a comprehensive assessment of the “miRNome” of ESCs cultured under conditions favoring ground-state pluripotency. We found that ground-state ESCs express a distinct set of miRNAs compared with ESCs grown in serum. Interestingly, most “ground-state miRNAs” are encoded by an imprinted region on chromosome 12 within the Dlk1-Dio3 locus. Functional analysis revealed that ground-state miRNAs embedded in the Dlk1-Dio3 locus (miR-541-5p, miR-410-3p, and miR-381-3p) promoted pluripotency via inhibition of multi-lineage differentiation and stimulation of self-renewal. Overall, our results demonstrate that ground-state pluripotency is associated with a unique miRNA signature, which supports ground-state self-renewal by suppressing differentiation.

Cell-free microRNAs (cfmiRNAs), also known as extracellular or secretory microRNAs, are an emerging class of miRNAs that are released or secreted by cells. These miRNAs are transferred through various body fluids. A growing body of research has recently revealed that cancer cells also secrete their distinctive cfmiRNAs to the extracellular environment highlighting the contribution of cfmiRNAs to cancer progression. CfmiRNAs show high stability in the body fluids. Three pathways have been proposed for their entry into the body fluids: passive release from broken, injured and dead cells; active secretion through microvesicles; and active secretion via microvesicle-free protein-dependent route. Active pathways seem to play leading roles in the delivery of miRNAs. Detection of cfmiRNAs is of particular relevance to their translation into the clinic. Much effort has been devoted to the development of highly sensitive and efficient approaches for detection purposes. Nevertheless, some barriers such as finding a unique internal control for all cancer types remain to be bypassed. This review aims to provide an insight into the promises represented by cfmiRNAs as cancer biomarkers and describes advances made in the identification of numerous types of extracellular miRNAs that have potential for use in the diagnosis of a variety of cancers.

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COVID-19 has currently become the biggest challenge in the world. There is still no specific medicine for COVID-19, which leaves a critical gap for the identification of new drug candidates for the disease. Recent studies have reported that the small-molecule enoxacin exerts an antiviral activity by enhancing the RNAi pathway. The aim of this study is to analyze if enoxacin can exert anti-SARS-CoV-2 effects. We exploit multiple computational tools and databases to examine (i) whether the RNAi mechanism, as the target pathway of enoxacin, could act on the SARS-CoV-2 genome, and (ii) microRNAs induced by enoxacin might directly silence viral components as well as the host cell proteins mediating the viral entry and replication. We find that the RNA genome of SARS-CoV-2 might be a suitable substrate for DICER activity. We also highlight several enoxacin-enhanced microRNAs which could target SARS-CoV-2 components, pro-inflammatory cytokines, host cell components facilitating viral replication, and transcription factors enriched in lung stem cells, thereby promoting their differentiation and lung regeneration. Finally, our analyses identify several enoxacin-targeted regulatory modules that were critically associated with exacerbation of the SARS-CoV-2 infection. Overall, our analysis suggests that enoxacin could be a promising candidate for COVID-19 treatment through enhancing the RNAi pathway.

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