• carrdiomyogenesis
• heart development
• non coding RNAs

• Humans
• Animals
• Myocytes, Cardiac/metabolism
• Myocytes, Cardiac/cytology
• RNA, Untranslated/genetics
• RNA, Untranslated/metabolism
• Cell Differentiation
• Gene Expression Regulation, Developmental
• Myocardium/metabolism
• Myocardium/cytology
• Heart/embryology
• Epigenesis, Genetic
• Cell Lineage

• biomarker
• doxorubicin-induced cardiotoxicity
• microRNA
• therapeutic target

• No. 82074254 National Natural Science Foundation of China

• Cell Differentiation
• Cells, Cultured
• Humans
• Mesenchymal Stem Cells
• Myocytes, Cardiac/metabolism
• Osteogenesis
• Signal Transduction

• cardiovascular disorders
• stem cell
• tissue engineering

Stem cell transplantation is one of most valuable methods in the treatment of myocardial infarction, and adipose-derived stem cells (ASCs) are becoming a hot topic in medical research. Previous studies have shown that ASCs can be differentiated into cardiomyocyte-like cells, but the efficiency and survival rates are low. We investigated the role and mechanism of microRNA-1 (miR-1) in the differentiation of ASCs into cardiomyocyte-like cells. ASCs and cardiomyocytes were isolated from neonatal rats. We constructed lentivirus for overexpressing miR-1 and used DAPT, an antagonist of the Notch1 pathway, for in vitro analyses. We performed cocultures with ASCs and cardiomyocytes. The differentiation efficiency of ASCs was detected by cell-specific surface antigens. Our results showed that miR-1 can promote the expression of Notch1 and reduce the expression of Hes1, a Notch pathway factor, and overexpression of miR-1 can promote the differentiation of ASCs into cardiomyocyte-like cells, which may occur by regulating Notch1 and Hes1.

• DNMT1
• hBMSCs
• miR-148a
• myocardial differentiation

• Cardiomyogenesis
• Human bone marrow-derived mesenchymal stem cells (hBM-MSCs)
• Lentiviral vectors
• MicroRNA-499a

• Cardiovascular development
• ESC
• Nodal cells
• Pacemaker
• Subtype differentiation
• System-based data analysis
• iPSC

• Hes1
• LncRNAs
• Neural stem cells
• UCA1
• miR-1

Embryonic stem (ES) and induced pluripotent stem (iPS) cells are attractive tools for regenerative medicine therapies. However, aberrant cell populations that display flattened morphology and lose ground-state pluripotency often appear spontaneously, unless glycogen synthase kinase 3β (GSK3β) and mitogen-activated protein kinase kinase (MEK1/2) are inactivated. Here, we show that membrane translocation of the t-SNARE protein syntaxin-4 possibly is involved in this phenomenon. We found that mouse ES cells cultured without GSK3β/MEK1/2 inhibitors (2i) spontaneously extrude syntaxin-4 at the cell surface and that artificial expression of cell surface syntaxin-4 induces appreciable morphological changes and mesodermal differentiation through dephosphorylation of Akt. Transcriptome analyses revealed several candidate elements responsible for this, specifically, an E-to P-cadherin switch and a marked downregulation of Zscan4 proteins, which are DNA-binding proteins essential for ES cell pluripotency. Embryonic carcinoma cell lines F9 and P19CL6, which maintain undifferentiated states independently of Zscan4 proteins, exhibited similar cellular behaviors upon stimulation with cell surface syntaxin-4. The functional ablation of E-cadherin and overexpression of P-cadherin reproduced syntaxin-4-induced cell morphology, demonstrating that the E- to P-cadherin switch executes morphological signals from cell surface syntaxin-4. Thus, spontaneous membrane translocation of syntaxin-4 emerged as a critical element for maintenance of the stem-cell niche.

• Heart
• Myocardial infarction
• miR-1
• miR-133a
• miR-208a/b
• miR-499

• Animals
• Calcium Signaling
• Cell Differentiation
• Embryonic Stem Cells/cytology
• Embryonic Stem Cells/metabolism
• Gene Expression Regulation
• Heart/embryology
• Heart/physiology
• Heart Diseases/diagnosis
• Heart Diseases/genetics
• Heart Diseases/physiopathology
• Humans
• MicroRNAs/genetics
• Myocardial Infarction/diagnosis
• Myocardial Infarction/genetics
• Myocardial Infarction/physiopathology
• Myocardium/cytology
• Myocardium/metabolism
• Myocytes, Cardiac/cytology
• Myocytes, Cardiac/metabolism
• Organ Specificity
• Oxidative Stress

The loss of cardiomyocytes during injury and disease can result in heart failure and sudden death, while the adult heart has a limited capacity for endogenous regeneration and repair. Current stem cell-based regenerative medicine approaches modestly improve cardiomyocyte survival, but offer neglectable cardiomyogenesis. This has prompted the need for methodological developments that crease de novo cardiomyocytes. Current insights in cardiac development on the processes and regulatory mechanisms in embryonic cardiomyocyte differentiation provide a basis to therapeutically induce these pathways to generate new cardiomyocytes. Here, we discuss the current knowledge on embryonic cardiomyocyte differentiation and the implementation of this knowledge in state-of-the-art protocols to the direct reprogramming of cardiac fibroblasts into de novo cardiomyocytes in vitro and in vivo with an emphasis on microRNA-mediated reprogramming. Additionally, we discuss current advances on state-of-the-art targeted drug delivery systems that can be employed to deliver these microRNAs to the damaged cardiac tissue. Together, the advances in our understanding of cardiac development, recent advances in microRNA-based therapeutics, and innovative drug delivery systems, highlight exciting opportunities for effective therapies for myocardial infarction and heart failure.

• Cardiac repair
• Cellular plasticity
• Targeted drug delivery
• MicroRNA
• Reprogramming

• MicroRNAs
• Transcription factors
• Transdifferentiation

Metastatic breast cancer remains a highly lethal disease, and it is very important to evaluate the biomarkers associated with the distant metastasis. MicroRNA (miRNA) are small non‐protein coding RNA that regulate various cellular functions. Recent investigations have demonstrated the importance of some miRNA in breast cancer, but the significance of the great majority of miRNA remains largely unclear in breast cancer metastasis. Therefore, in this study, we first examined expression profiles of miRNA in stage IV breast carcinoma tissues, comparing stage I–III cases by miRNA PCR array, and identified miR‐1 as the miRNA which was the most associated with the distant metastasis. However, miR‐1 has not yet been examined in breast carcinoma tissue, and its significance remains unknown. Therefore, we further examined miR‐1 expression in breast carcinoma using in situ hybridization (ISH). miR‐1 was localized in carcinoma cells in 20% of breast carcinoma cases, but it was negligible in non‐neoplastic mammary glands or stroma. miR‐1 ISH status was significantly associated with stage, pathological T factor, lymph node metastasis, distant metastasis, histological grade, estrogen receptor, progesterone receptor and Ki‐67 in breast carcinoma. Moreover, the miR‐1 status was demonstrated using multivariate analysis as an independent worse prognostic factor for both disease‐free and breast cancer‐specific survival. These findings suggest that abnormal miR‐1 expression is associated with an aggressive phenotype of breast carcinoma and that miR‐1 status is a potent prognostic factor in human breast cancer patients.

• Breast cancer
• PCR array
• in situ hybridization
• microRNA
• prognosis

MicroRNAs are small non-coding RNAs that participate in different biological processes, providing subtle combinational regulation of cellular pathways, often by regulating components of signalling pathways. Aberrant expression of miRNAs is an important factor in the development and progression of disease. The canonical myomiRs (miR-1, -133 and -206) are central to the development and health of mammalian skeletal and cardiac muscles, but new findings show they have regulatory roles in the development of other mammalian non-muscle tissues, including nerve, brain structures, adipose and some specialised immunological cells. Moreover, the deregulation of myomiR expression is associated with a variety of different cancers, where typically they have tumor suppressor functions, although examples of an oncogenic role illustrate their diverse function in different cell environments. This review examines the involvement of the related myomiRs at the crossroads between cell development/tissue regeneration/tissue inflammation responses, and cancer development.

• Muscle microRNAs
• MiR-1
• MiR-206
• MiR-133a
• MiR-133b
• Cell development
• Cancer

• R01 AA022701 NIAAA NIH HHS

• Cell transplantation
• Chronic heart disease
• Hematopoietic cell transplantation
• Hematopoietic cells

• MicroRNA
• Non-viral vector
• Regenerative medicine
• Scaffold
• Stem cells
• Tissue engineering
• Viral vector

The tumor suppressor adenomatous polyposis coli (APC) is mutated in sporadic and familial colorectal tumors. APC stimulates the activity of the Cdc42- and Rac1-specific guanine nucleotide exchange factor Asef and promotes the migration and invasion of colorectal tumor cells. Furthermore, Asef is overexpressed in colorectal tumors and is required for colorectal tumorigenesis. It is also known that NOTCH signaling plays critical roles in colorectal tumorigenesis and fate determination of intestinal progenitor cells. Here we show that NOTCH3 up-regulates Asef expression by activating the Asef promoter in colorectal tumor cells. Moreover, we demonstrate that microRNA-1 (miR-1) is down-regulated in colorectal tumors and that miR-1 has the potential to suppress NOTCH3 expression through direct binding to its 3’-UTR region. These results suggest that the miR-1-NOTCH3-Asef pathway is important for colorectal tumor cell migration and may be a promising molecular target for the treatment of colorectal tumors.

• 3' Untranslated Regions/genetics
• Caco-2 Cells
• Cell Line
• Cell Movement/genetics
• Cell Movement/physiology
• Chromatin Immunoprecipitation
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/metabolism
• Humans
• In Vitro Techniques
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Protein Binding
• Receptor, Notch3
• Receptors, Notch/genetics
• Receptors, Notch/metabolism
• Signal Transduction/genetics
• Signal Transduction/physiology

Mounting evidence in stem cell biology has shown that microRNAs (miRNAs) play a crucial role in cell fate specification, including stem cell self-renewal, lineage-specific differentiation, and somatic cell reprogramming. These functions are tightly regulated by specific gene expression patterns that involve miRNAs and transcription factors. To maintain stem cell pluripotency, specific miRNAs suppress transcription factors that promote differentiation, whereas to initiate differentiation, lineage-specific miRNAs are upregulated via the inhibition of transcription factors that promote self-renewal. Small molecules can be used in a similar manner as natural miRNAs, and a number of natural and synthetic small molecules have been isolated and developed to regulate stem cell fate. Using miRNAs as novel regulators of stem cell fate will provide insight into stem cell biology and aid in understanding the molecular mechanisms and crosstalk between miRNAs and stem cells. Ultimately, advances in the regulation of stem cell fate will contribute to the development of effective medical therapies for tissue repair and regeneration. This review summarizes the current insights into stem cell fate determination by miRNAs with a focus on stem cell self-renewal, differentiation, and reprogramming. Small molecules that control stem cell fate are also highlighted.

• MicroRNA
• Stem cell fate
• Differentiation
• Self-renewal
• Reprogramming
• Small molecule