miR-21-containing microvesicles from injured tubular epithelial cells promote tubular phenotype transition by targeting PTEN protein.

Renal fibrosis is inevitably progressive no matter what the initial insult is or whether the insult persists. In an experimental fibrosis model induced by unilateral ureteral obstruction, the accelerated pathological changes could hardly be explained by aggravated pressure caused by hydronephrosis after ligation. Moreover, at the initial stage, tubular phenotype transition and matrix deposition in obstructive kidneys are always local and scattered; however, these renal lesions expand and progress with time.

Protein tyrosine phosphatase 1B deficiency ameliorates murine experimental colitis via the expansion of myeloid-derived suppressor cells.

Protein tyrosine phosphatase 1B (PTP1B) is a key molecule in modulating low-degree inflammatory conditions such as diabetes. The role of PTP1B in other chronic inflammations, however, remains unknown. Here, we report that PTP1B deficiency ameliorates Dextran Sulfate Sodium (DSS)-induced murine experimental colitis via expanding CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs).

The identification of novel targets of miR-16 and characterization of their biological functions in cancer cells.

Background: In eukaryotes, miR-16 is an important microRNA (miRNA) that is involved in numerous biological processes. However, it is not fully understood how miR-16 executes its physiological functions. In the present study, we aimed to identify novel miR-16 targets and study their biological functions.

Potential microRNA targets for cancer chemotherapy.

MicroRNA (miRNA) is an important type of non-coding RNAs with both physiological and pathological functions in human beings. Aberrant expression of miRNAs has been found in tumor tissues and the expression profile of certain groups of miRNAs is now emerging as bio-marker for cancer. It has been confirmed that miRNAs can exert oncogenic or tumor-suppressive functions through repressing the expression of their target genes which play different roles in tumorigenesis.

Microvesicle-mediated transfer of microRNA-150 from monocytes to endothelial cells promotes angiogenesis.

Recent studies by our group and others show that microRNAs can be actively secreted into the extracellular environment through microvesicles (MVs) and function as secretory signaling molecules that influence the recipient cell phenotypes. Here we investigate the role of monocyte-secreted miR-150 in promoting the capillary tube formation of endothelial cells and in enhancing angiogenesis. In vitro capillary tube formation and in vivo angiogenesis assays showed that monocyte-derived MVs have strong pro-angiogenic activities.

Nuclear microRNAs and their unconventional role in regulating non-coding RNAs.

MicroRNAs (miRNAs) are small non-coding RNAs (ncRNAs) that are involved in post-transcriptional gene regulation. It has long been assumed that miRNAs exert their roles only in the cytoplasm, where they recognize their target protein-coding messenger RNAs (mRNAs), and result in translational repression or target mRNA degradation. Recent studies, however, have revealed that mature miRNAs can also be transported from the cytoplasm to the nucleus and that these nuclear miRNAs can function in an unconventional manner to regulate the biogenesis and functions of ncRNAs (including miRNAs and long ncRNAs), adding a new layer of complexity to our understanding of gene regulation.

MicroRNA-17/20a/106a modulate macrophage inflammatory responses through targeting signal-regulatory protein α.

Background: Signal-regulatory protein α (SIRPα) is an essential signaling molecule that modulates leukocyte inflammatory responses. However, the regulation of selective SIRPα synthesis and its dynamic changes in leukocytes under inflammatory stimulation remain incompletely understood.

Objective: We sought to identify the microRNAs (miRNAs) that posttranscriptionally regulate SIRPα synthesis and their roles in modulating macrophage inflammatory responses.

microRNAs are ligands of Toll-like receptors.

It has long been known that microRNAs (miRNAs) can regulate target gene expression at the post-transcriptional level. Recent studies, however, have revealed that miRNAs can also be transported from donor cells to recipient cells, in which these RNAs function in a novel manner as ligands of Toll-like receptors. Here, we review the latest findings on these unconventional miRNAs, with special emphasis on their biological significance.

Elevated serum β2-glycoprotein-I-lipoprotein(a) complexes levels are associated with the presence and complications in type 2 diabetes mellitus.

Aims: To examine the serum levels of β2-glycoprotein I-lipoprotein(a) complexes [β2-GPI-Lp(a)] in type 2 diabetes mellitus (T2DM) patients and evaluate the association of the complexes with complications in T2DM.

Methods: Fifty two T2DM patients (22 with complications and 30 free of complications) and 52 age/gender-matched healthy controls were studied. Serum concentrations of β2-GPI-Lp(a) and ox-Lp(a) were measured by "sandwich" ELISAs and their associations with complications were examined using multiple linear regression.

Immune modulatory function of abundant immune-related microRNAs in microvesicles from bovine colostrum.

Colostrum provides essential nutrients and immunologically active factors that are beneficial to newborns. Our previous work demonstrated that milk contains large amounts of miRNA that is largely stored in milk-derived microvesicles (MVs). In the present study, we found that the MVs from colostrum contain significantly higher levels of several immune-related miRNAs.

New roles for microRNAs in cross-species communication.

Communication between cells ensures coordinated behavior. In prokaryotes, this signaling is typically referred to as quorum sensing, whereas in eukaryotic cells, communication occurs through hormones. In recent years, reports have shown that small noncoding RNAs, called microRNAs (miRNAs), can be transmitted from one species to another, inducing signal interference in distant species, even in a cross-kingdom manner.

Increased serum and urinary microRNAs in children with idiopathic nephrotic syndrome.

Background: MicroRNAs (miRNAs) are present in body fluids and may have the potential to serve as disease biomarkers. This study explored the clinical value of miRNAs in serum and urine as biomarkers for idiopathic childhood nephrotic syndrome (NS).

Methods: We obtained serum samples from 159 NS children (24 steroid resistant and 135 steroid sensitive), 109 age/sex-matched healthy controls and 44 children with other kidney diseases.

MicroRNA-31 activates the RAS pathway and functions as an oncogenic MicroRNA in human colorectal cancer by repressing RAS p21 GTPase activating protein 1 (RASA1).

MicroRNAs (miRNAs) are known to play a vital role in colorectal cancer. We found a widespread disruption in miRNA expression during colorectal tumorigenesis using microarray and quantitative RT-PCR analysis; of the 161 miRNAs altered in colorectal cancer compared with normal adjacent tissue samples, miR-31 was the most significantly dysregulated. We identified candidate targets of miR-31 using bioinformatics approaches and validated RAS p21 GTPase activating protein 1 (RASA1) as a direct target.

Urinary microRNA-10a and microRNA-30d serve as novel, sensitive and specific biomarkers for kidney injury.

The steadily increasing incidence of kidney injury is a significant threat to human health. The current tools available for the early detection of kidney injury, however, have limited sensitivity or specificity. Thus, the development of novel biomarkers to detect early kidney injury is of high importance.

Argonaute 2 complexes selectively protect the circulating microRNAs in cell-secreted microvesicles.

Cell-secreted miRNAs are highly stable and can serve as biomarkers for various diseases and signaling molecules in intercellular communication. The mechanism underlying the stability of circulating miRNAs, however, remains incompletely understood. Here we show that Argonaute 2 (Ago2) complexes and microvesicles (MVs) provide specific and non-specific protection for miRNA in cell-secreted MVs, respectively.

miRNA regulates noncoding RNA: a noncanonical function model.

It has long been assumed that miRNAs can only target protein-coding mRNAs in the cytoplasm. Recent studies, however, reveal miRNAs are also transported from the cytoplasm to the nucleus, where they function in a noncanonical manner to regulate noncoding RNAs. Here, we highlight the working model of these noncanonical miRNAs.

Genipin inhibits mitochondrial uncoupling protein 2 expression and ameliorates podocyte injury in diabetic mice.

Diabetic nephropathy (DN) is one of the most common causes of end stage renal disease (ESRD) in China, which requires renal replacement therapy. Recent investigations have suggested an essential role of podocyte injury in the initial stage of DN. This study investigated the potential therapeutic role of genipin, an active extract from a traditional Chinese medicine, on progression of DN in diabetic mice induced by intraperitoneally injection of streptozocin (STZ).

Circulating levels of microRNA from children with newly diagnosed type 1 diabetes and healthy controls: evidence that miR-25 associates to residual beta-cell function and glycaemic control during disease progression.

This study aims to identify key miRNAs in circulation, which predict ongoing beta-cell destruction and regeneration in children with newly diagnosed Type 1 Diabetes (T1D). We compared expression level of sera miRNAs from new onset T1D children and age-matched healthy controls and related the miRNAs expression levels to beta-cell function and glycaemic control. Global miRNA sequencing analyses were performed on sera pools from two T1D cohorts (n = 275 and 129, resp.

Effective inhibition of cytomegalovirus infection by external guide sequences in mice.

Ribonuclease P complexed with external guide sequence (EGS) bound to mRNA represents a unique nucleic acid-based gene interference approach for modulation of gene expression. Compared with other strategies, such as RNA interference, the EGS-based technology is unique because a custom-designed EGS molecule can hybridize with any mRNA and recruit intracellular ribonuclease P for specific degradation of the target mRNA. It has not been reported whether the EGS-based technology can modulate gene expression in mice.

Brain-selective kinase 2 (BRSK2) phosphorylation on PCTAIRE1 negatively regulates glucose-stimulated insulin secretion in pancreatic β-cells.

Brain-selective kinase 2 (BRSK2) has been shown to play an essential role in neuronal polarization. In the present study, we show that BRSK2 is also abundantly expressed in pancreatic islets and MIN6 β-cell line. Yeast two-hybrid screening, GST fusion protein pull-down, and co-immunoprecipitation assays reveal that BRSK2 interacts with CDK-related protein kinase PCTAIRE1, a kinase involved in neurite outgrowth and neurotransmitter release.

Regulation of mammalian gene expression by exogenous microRNAs.

Communication between cells ensures coordination of behavior. In prokaryotes, this signaling is usually referred to as quorum sensing, while eukaryotic cells communicate through hormones. In recent years, a growing number of reports have shown that small signaling molecules produced by organisms from different kingdoms of nature can facilitate cross-talk, communication, or signal interference.

Identification of seven serum microRNAs from a genome-wide serum microRNA expression profile as potential noninvasive biomarkers for malignant astrocytomas.

The involvement of circulating microRNAs (miRNAs) in cancer and their potential as biomarkers of diagnosis and prognosis are becoming increasingly appreciated; however, little is known about circulating miRNA profiles in astrocytomas. In our study, we performed genome-wide serum miRNA analysis by the Solexa sequencing followed by validation conducted in the training and verification sets with a stem-loop quantitative reverse-transcription PCR (RT-qPCR) assay from serum samples of 122 untreated astrocytomas patients (WHO grades III-IV) and 123 normal controls. Identified miRNAs were subsequently examined in 55 grade II, 15 grade I astrocytomas, 11 astrogliosis, 42 other primary brain tumors and 8 tumor tissues from grades II-IV astrocytomas.

A panel of serum microRNAs as specific biomarkers for diagnosis of compound- and herb-induced liver injury in rats.

Background: Drug-induced liver injury (DILI) has been a public, economic and pharmaceutical issue for many years. Enormous effort has been made for discovering and developing novel biomarkers for diagnosing and monitoring both clinical and preclinical DILI at an early stage, though progress has been relatively slow. Additionally, herb-induced liver injury is an emerging cause of liver disease because herbal medicines are increasingly being used worldwide.