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MicroRNAs (miRs) are small noncoding RNAs that play important roles in both physiological and pathological processes through post‐transcriptional regulation. The miR‐17‐92 cluster includes six individual members: miR‐17, miR‐18a, miR‐19a, miR‐19b‐1, miR‐20a, and miR‐92a‐1. The miR‐17‐92 cluster has been extensively studied and reported to broadly function in cancer biology, immunology, neurology, pulmonology, and cardiology. This review focuses on its roles in heart development and cardiac diseases. We briefly introduce the nature of the miR‐17‐92 cluster and its crucial roles in both normal development and the pathogenesis of various diseases. We summarize the recent progress in understanding the versatile roles of miR‐17‐92 during cardiac development, regeneration, and aging. Additionally, we highlight the indispensable roles of the miR‐17‐92 cluster in pathogenesis and therapeutic potential in cardiac birth defects and adult cardiac diseases. [ABSTRACT FROM AUTHOR]

miR-17-92 cluster encodes six micro RNAs (miRNAs) and plays a crucial role in the regulation of various cellular processes. Aberrant expression of this cluster may result in the onset of several diseases. Initially, the role of miR-17-92 cluster in tumorigenesis was discovered but recent research has also uncovered its role in other diseases. Members of the cluster may serve as potential biomarkers in the prognosis, diagnosis, and treatment of several diseases and their complications. In this article, we have reviewed the recent research carried out on the expression pattern of miR-17-92 cluster in non-communicable diseases i.e., obesity, cardiovascular diseases (CVD), kidney diseases (KD) and diabetes mellitus (DM). We examined miR-17-92 role in pathological processes and their potential importance as biomarkers. Each member of the cluster miR-17-92 was upregulated in obesity. miR-18a, miR-19b-3p, miR20a, and miR92a were significantly upregulated in CVD. An equal fraction of the cluster was dysregulated (upregulated and downregulated) in diabetes; however, miR-17-92 was downregulated in most studies on CKD. [ABSTRACT FROM AUTHOR]

MicroRNA (miRNA) biogenesis is tightly regulated to maintain distinct miRNA expression patterns. Almost half of mammalian miRNAs are generated from miRNA clusters, but this process is not well understood. We show here that Serine‐arginine rich splicing factor 3 (SRSF3) controls the processing of miR‐17‐92 cluster miRNAs in pluripotent and cancer cells. SRSF3 binding to multiple CNNC motifs downstream of Drosha cleavage sites within miR‐17‐92 is required for the efficient processing of the cluster. SRSF3 depletion specifically compromises the processing of two paralog miRNAs, miR‐17 and miR‐20a. In addition to SRSF3 binding to the CNNC sites, the SRSF3 RS‐domain is essential for miR‐17‐92 processing. SHAPE‐MaP probing demonstrates that SRSF3 binding disrupts local and distant base pairing, resulting in global changes in miR‐17‐92 RNA structure. Our data suggest a model where SRSF3 binding, and potentially its RS‐domain interactions, may facilitate an RNA structure that promotes miR‐17‐92 processing. SRSF3‐mediated increase in miR‐17/20a levels inhibits the cell cycle inhibitor p21, promoting self‐renewal in normal and cancer cells. The SRSF3‐miR‐17‐92‐p21 pathway operates in colorectal cancer, linking SRSF3‐mediated pri‐miRNA processing and cancer pathogenesis. Synopsis: SRSF3 binds to CNNC motifs within the miR‐17‐92 cluster and promotes the processing of specific cluster miRNAs. SRSF3 binding changes miR‐17‐92 structure, and this may impact miR‐17‐92 processing. Both SRSF3 binding to multiple positions within the miR‐17‐92 cluster RNA and the SRSF3 RS‐domain are required for the processing of cluster miRNAs.SHAPE‐MaP analyses demonstrate that SRSF3 binding to miR‐17‐92 alters its secondary structure.SRSF3‐mediated increase in miR‐17/20a levels promotes self‐renewal by inhibiting the cell cycle inhibitor p21 and marks advance colorectal cancer, linking SRSF3‐mediated pri‐miRNA processing to cancer pathogenesis. [ABSTRACT FROM AUTHOR]

Induced pluripotent stem cells (iPSCs) are promising cell sources for regenerative medicine and disease modeling. iPSCs are commonly established by introducing the defined reprogramming factors Oct4, Sox2, Klf4, and c-Myc. However, iPSC reprogramming efficiency remains low. Although recent studies have identified microRNAs that contribute to efficient reprogramming, the underlying molecular mechanisms are not completely understood. miR-17-92 is highly expressed in embryonic stem cells and may play an important role in regulating stem cell properties. Therefore, we examined the role of miR-17-92 in the induction of mouse iPSC production. c-Myc-mediated miR-17-92 upregulation increased reprogramming efficiency, whereas CRISPR/Cas9-based deletion of the miR-17-92 cluster decreased reprogramming efficiency. A combination of in silico and microarray analyses revealed that Pten and cyclin-dependent kinase inhibitor 1 (known as p21) are common target genes of miR-17 and miR-20a, which are transcribed from the miR-17-92 cluster. Moreover, miR-17-92 downregulated p21 in the early phase and PTEN in the mid-to-late phase of reprogramming. These downregulations were perturbed by introducing the 3′ UTR of PTEN and p21, respectively, suggesting that PTEN and p21 mRNAs are competing endogenous RNAs (ceRNA) against miR-17-92. Collectively, we propose that the c-Myc-mediated expression of miR-17-92 is involved in iPSC reprogramming through the phase-dependent inhibition of PTEN and p21 in a ceRNA manner, thus elucidating an underlying mechanism of iPSC reprogramming. [ABSTRACT FROM AUTHOR]

Gain of chromosome arm 13q is one of the most prevalent DNA copy number alterations associated with colorectal adenoma-to-carcinoma progression. The oncogenic miR-17-92 cluster, located at 13q, was found to be overexpressed in colorectal cancer and in adenomas harboring 13q gain. However, to what extent overexpression of this group of microRNAs actually drives progression to cancer remains to be resolved. Therefore, we aimed to clarify the role of miR-17-92 cluster in the progression from colorectal adenoma to carcinoma.The miR-17-92 cluster was overexpressed in human colorectal adenoma organoids without 13q gain and downstream effects on mRNA expression were investigated, along with functional consequences in vitro and in vivo.Comparison of mRNA sequencing results of organoids overexpressing miR-17-92 and cultures transduced with control vector revealed a miR-17-92 expression signature. This signature appeared to be enriched in an independent series of colorectal cancers and adenomas with 13q gain, confirming that miR-17-92 expression is associated with malignant progression. However, tumor-associated characteristics, such as increased proliferation rate, were not observed in miR-17-92 overexpressing adenoma organoids in vitro. In addition, subcutaneous injection of these organoids in immunodeficient mice was insufficient to cause tumor outgrowth.In conclusion, this study showed that miR-17-92 expression contributes to 13q gain-associated adenoma-to-carcinoma progression, however, this is insufficient to cause malignancy.

Induced pluripotent stem cells (iPSCs) are promising cell sources for regenerative medicine and disease modeling. iPSCs are commonly established by introducing the defined reprogramming factors Oct4, Sox2, Klf4, and c-Myc. However, iPSC reprogramming efficiency remains low. Although recent studies have identified microRNAs that contribute to efficient reprogramming, the underlying molecular mechanisms are not completely understood. miR-17-92 is highly expressed in embryonic stem cells and may play an important role in regulating stem cell properties. Therefore, we examined the role of miR-17-92 in the induction of mouse iPSC production. c-Myc-mediated miR-17-92 upregulation increased reprogramming efficiency, whereas CRISPR/Cas9-based deletion of the miR-17-92 cluster decreased reprogramming efficiency. A combination of in silico and microarray analyses revealed that Pten and cyclin-dependent kinase inhibitor 1 (known as p21) are common target genes of miR-17 and miR-20a, which are transcribed from the miR-17-92 cluster. Moreover, miR-17-92 downregulated p21 in the early phase and PTEN in the mid-to-late phase of reprogramming. These downregulations were perturbed by introducing the 3′ UTR of PTEN and p21, respectively, suggesting that PTEN and p21 mRNAs are competing endogenous RNAs (ceRNA) against miR-17-92. Collectively, we propose that the c-Myc-mediated expression of miR-17-92 is involved in iPSC reprogramming through the phase-dependent inhibition of PTEN and p21 in a ceRNA manner, thus elucidating an underlying mechanism of iPSC reprogramming.

Non-coding RNAs that are small in size, called microRNAs (miRNAs), exert a consequence in neutralizing gene activity after transcription. The nervous system is a massively expressed organ, and an expanding body of research reveals the vital functions that miRNAs play in the brain's growth and neural activity. The significant benefit of miRNAs on the development of the central nervous system is currently shown through new scientific methods that concentrate on targeting and eradicating vital miRNA biogenesis pathways the elements involving Dicer and DGCR8. Modulation of miRNA has been associated with numerous essential cellular processes on neural progenitors, like differentiation, proliferation, and destiny determination. Current research discoveries that emphasize the significance of miRNAs in the complex process of brain development are included in this book. The miRNA pathway plays a major role in brain development, its operational dynamics, and even diseases. Recent studies on miRNA-mediated gene regulation within neural discrepancy, the circadian period and synaptic remodeling are signs of this. We also discussed how these discoveries may affect our comprehension of the fundamental processes behind brain diseases, highlighting the novel therapeutic opportunities miRNAs provide for treating various human illnesses., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Wound healing is a complex and dynamic process that involves a series of cellular and molecular events. Mesenchymal stem cells (MSCs) and their exosomes (MSC-Exos) have crucial functions in cutaneous wound healing. MiR-17–92 is a multifunctional microRNA (miRNA) cluster that plays vital roles in tissue development and tumor angiogenesis. This study aimed to explore the function of miR-17.92 in wound healing as a component of MSC-Exos. Human MSCs were cultured in serum-free medium, and exosomes were collected by ultracentrifugation. The levels of miR-17–92 in MSCs and MSC-Exos were determined by quantitative real-time polymerase chain reaction. MSC-Exos were topically applied to full-thickness excision wounds in the skin of miR-17–92 knockout (KO) and wild-type (WT) mice. The proangiogenic and antiferroptotic effects of MSC-Exos overexpressing miR-17–92 were assayed by evaluating the relative levels of angiogenic and ferroptotic markers. MiRNA-17–92 was found to be highly expressed in MSCs and enriched in MSC-Exos. Moreover, MSC-Exos promoted the proliferation and migration of human umbilical vein endothelial cells in vitro. KO of miR-17–92 effectively attenuated the promotion of wound healing by MSC-Exos. Furthermore, exosomes derived from miR-17–92-overexpressing human umbilical cord-derived MSCs accelerated cell proliferation, migration, angiogenesis, and enhanced against erastin-induced ferroptosis in vitro. miR-17–92 plays a key role in the protective effects of MSC-Exos against erastin-induced ferroptosis in HUVECs These findings suggest that miR-17–92 participates in the repair ability of MSC-Exos and that miR-17–92-overexpressing exosomes may represent a new strategy for cutaneous wound repair. • Mesenchymal stem cells (MSCs) and its exosomes (MSC-Exos) have crucial functions in cutaneous wound healing. • MiR-17–92 is a multifunctional microRNA (miRNA) cluster that plays vital roles in tissue development and tumour angiogenesis. • MSC-exosomal miR-17–92 promotes wound healing by inducing angiogenesis and inhibiting ferroptosis. Additionally, MiR-17–92 is a multifunctional microRNA (miRNA) cluster that plays vital roles in tissue development and tumour angiogenesis. [ABSTRACT FROM AUTHOR]

Chronic myeloid leukemia accounts for human deaths worldwide and could enhance sevenfold by 2050. Thus, the treatment regimen for this disorder is highly crucial at this time. Flavaglines are a natural class of cyclopentane benzofurans exhibiting various bioactivities like anticancer action. Despite the antiproliferative activity of flavaglines against diverse cancer cells, their roles and mechanism of action in chronic myeloid leukemia (CML) remain poorly understood. Thus, this study examines the antiproliferative effect of a newly synthesized flavagline derivative, 1-chloracetylrocaglaol (A2074), on erythroleukemia K562 cells and the zebrafish xenograft model. The study revealed that A2074 could inhibit proliferation, promote apoptosis, and boost megakaryocyte differentiation of K562 cells. This flavagline downregulated c-MYC and miR-17-92 cluster genes, targeting upregulation of the apoptotic protein Bcl-2-like protein 11 (BIM). The work uncovered a critical role of the c-MYC-miR-17-92-BIM axis in the growth and survival of CML cells., (© 2022 Deutsche Pharmazeutische Gesellschaft.)