microRNA Function Research Articles

RETRACTED: Sevoflurane up-regulates microRNA-204 to ameliorate myocardial ischemia/reperfusion injury in mice by suppressing Cotl1

The inhaled sevoflurane (sevo) is known to protect against myocardial ischemia/reperfusion (I/R) injury (MIRI), in which the functions of microRNAs (miRNAs) have been uncovered. However, the effect of sevo regulating miR-204 on this disease remains unknown. This research aims to explore the roles of sevo and miR-204 in the progression of MIRI. The MIRI mice models induced by coronary artery ligation were treated by sevo, miR-204 mimics or silenced coactosin-like protein-1 (Cotl1). The pathology of mice myocardial tissues, apoptosis and ultrastructure of cardiomyocytes were observed. The expression of miR-204, Cotl1, Bax and Bcl-2 was determined. The contents of oxidative stress-related factors and inflammatory factors in mouse myocardial tissues were assessed, and the serum levels of indicators that correlated with myocardial infarction were determined as well. The target relation between miR-204 and Cotl1 was confirmed. MiR-204 was down-regulated, and Cotl1 was up-regulated in myocardial tissues of MIRI mice, and Cotl1 was targeted by miR-204. Sevo, elevated miR-204 and inhibited Cotl1 could promote cardiac function of MIRI mice, and protect myocardial tissue against MIRI by repressing the cardiomyocyte apoptosis, oxidative stress and inflammation reaction in MIRI mice. We found that sevo could up-regulate miR-204 to ameliorate MIRI in mice by inhibiting Cotl1 expression, which may provide candidates for the MIRI treatment.

Macronutrient modulation of mRNA and microRNA function in animals: A review.

Dietary macronutrients have been regarded as a basic source of energy and amino acids that are necessary for the maintenance of cellular homeostasis, metabolic programming as well as protein synthesis. Due to the emergence of “nutrigenomics”, a unique discipline that combines nutritional and omics technologies to study the impacts of nutrition on genomics, it is increasingly evident that macronutrients also have a significant role in the gene expression regulation. Gene expression is a complex phenomenon controlled by several signaling pathways and could be influenced by a wide variety of environmental and physiological factors. Dietary macronutrients are the most important environmental factor influencing the expression of both genes and microRNAs (miRNA). miRNA are tiny molecules of 18 to 22 nucleotides long that regulate the expression of genes. Therefore, dietary macronutrients can influence the expression of genes in both direct and indirect manners. Recent advancements in the state-of-the-art technologies regarding molecular genetics, such as next-generation sequencing, quantitative PCR array, and microarray, allowed us to investigate the occurrence of genome-wide changes in the expression of genes in relation to augmented or reduced dietary macronutrient intake. The purpose of this review is to accumulate the current knowledge focusing on macronutrient mediated changes in the gene function. This review will discuss the impact of altered dietary carbohydrate, protein, and fat intake on the expression of coding genes and their functions. In addition, it will also summarize the regulation of miRNA, both cellular and extracellular miRNA, expression modulated by dietary macronutrients.

Cow milk exosomes activate NK cells and γδT cells in human PBMCs in vitro

Cow milk is a nourishing food containing numerous essential nutrients. In Japan, the consumption of cow milk is thought to enhance resistance to exhaustion-related diseases. Although several nutrients in cow milk, such as lactoferrin, are thought to modulate immune cells, the mechanisms remain unclear. Recently, the immunoregulatory functions of food-derived microRNAs or exosomes have been reported. Therefore, we studied the effects of exosomes derived from cow milk (CM-Exs) on immune cells in the present study. We obtained blood samples from healthy adult donors with the approval of the ethics committee. Peripheral blood mononuclear cells (PBMCs) were stimulated with CM-Exs in the absence or presence of interleukin-2 (IL-2) and IL-12. Cell surface markers and intracellular cytokine production were analysed by flow cytometry. CM-Ex stimulation enhanced the expression of CD69 on NK cells. Although CM-Ex stimulation alone did not induce interferon-γ (IFN-γ) production by NK cells or γδT cells, simultaneous stimulation with CM-Ex, IL-2 and IL-12 significantly enhanced IFN-γ production. In conclusion, cow milk consumption alone may not activate immune cells; however, CM-Exs could enhance immune cells under inflammatory conditions.

MicroRNA-574-3p inhibits the malignant behavior of liver cancer cells by targeting ADAM28.

Liver cancer is one of the most common and aggressive tumors, and usually leads to a poor clinical outcome. Increasing evidence has demonstrated the important functions of microRNAs (miRs) in tumor progression. miR-574-3p has been reported as a tumor suppressor and potential therapeutic target in various types of cancer. However, the underlying mechanism of the effects of miR-574-3p in liver cancer remains unknown. In the present study, reverse transcription-quantitative PCR was performed to detect miR-574-3p expression in liver cancer tissues, and the influence of miR-574-3p on cell growth was evaluated using the Cell Counting Kit-8 assay, and cell migration and flow cytometry analyses. The present study revealed that miR-574-3p expression was downregulated in liver cancer tissues and cell lines. miR-574-3p overexpression, achieved by transfecting miR-574-3p mimics into liver cancer cells, reduced cell proliferation and migration, and promoted cell apoptosis. Mechanistically, ADAM metallopeptidase domain 28 (ADAM28) was identified as a miR-574-3p target via binding to the 3'-untranslated region of the ADAM28 mRNA. Gain-of-function of miR-574-3p downregulated the expression levels of ADAM28 in liver cancer cells. Additionally, overexpression of ADAM28 significantly attenuated the suppressive effect of miR-574-3p on the growth of liver cancer cells. The present results provide novel insights into the function of the miR-574-3p/ADAM28 signaling pathway in liver cancer.

Predicting microRNA-disease associations from lncRNA-microRNA interactions via Multiview Multitask Learning.

Identifying microRNAs that are associated with different diseases as biomarkers is a problem of great medical significance. Existing computational methods for uncovering such microRNA-diseases associations (MDAs) are mostly developed under the assumption that similar microRNAs tend to associate with similar diseases. Since such an assumption is not always valid, these methods may not always be applicable to all kinds of MDAs. Considering that the relationship between long noncoding RNA (lncRNA) and different diseases and the co-regulation relationships between the biological functions of lncRNA and microRNA have been established, we propose here a multiview multitask method to make use of the known lncRNA-microRNA interaction to predict MDAs on a large scale. The investigation is performed in the absence of complete information of microRNAs and any similarity measurement for it and to the best knowledge, the work represents the first ever attempt to discover MDAs based on lncRNA-microRNA interactions. In this paper, we propose to develop a deep learning model called MVMTMDA that can create a multiview representation of microRNAs. The model is trained based on an end-to-end multitasking approach to machine learning so that, based on it, missing data in the side information can be determined automatically. Experimental results show that the proposed model yields an average area under ROC curve of 0.8410+/-0.018, 0.8512+/-0.012 and 0.8521+/-0.008 when k is set to 2, 5 and 10, respectively. In addition, we also propose here a statistical approach to predicting lncRNA-disease associations based on these associations and the MDA discovered using MVMTMDA. Python code and the datasets used in our studies are made available at https://github.com/yahuang1991polyu/MVMTMDA/.

Functional microRNA screening for dietary vitamin E regulation of abdominal fat deposition in broilers

ABSTRACT 1. Functional microRNA (miRNA) screening for abdominal fat tissue with different dietary vitamin E (VE) levels was performed to reveal miRNAs, genes and metabolic pathways involved in abdominal fat deposition in broilers. 2. A total of 240, one-day-old healthy female chicks were randomly allocated into five dietary treatments containing either 0, 20, 50, 75 or 100 IU DL-α-tocopherol acetate. The sequencing of miRNAs from abdominal fat tissues was performed. The target genes of miRNAs were predicted and enrichment analysis for these genes was performed. Diets supplemented with 50 IU VE significantly diminished abdominal fat deposition in broilers at day 35 of age. 3. A total of 29 miRNAs were differentially expressed between control and 50 IU VE treatment. Ten of the 23 target genes were enriched in four signalling pathways: tight junction, SNARE interactions in vesicular transport, regulation of autophagy and proteasome. 4. This study identified miRNA, target genes and pathways in dietary VE treatment for broilers, providing new insights into the miRNA regulation of abdominal fat deposition in broilers.

Plasma exosomal miR-125a-5p and miR-141-5p as non-invasive biomarkers for prostate cancer.

Predictive biomarkers for early diagnosis of prostate cancer are important for its treatment. The functional microRNAs in the exosomes of plasma and serum samples are of interest as stable and non-invasive biomarkers for recurrence in cancer patients. The present study aimed to clarify the value of plasma exosomal miRNA-125a-5p and miR-141-5p as biomarkers for the diagnosis of prostate cancer. The study included 19 healthy individuals and 31 prostate cancer patients. In comparison to the levels in healthy controls, exosomal miR-141-5p levels showed a slight increase in prostate cancer patients (p=0.085), and miR-125a-5p levels that showed a significant decrease in patients with prostate cancer than in healthy controls (p=0.032). As a derived parameter, the miR-125a-5p/miR-141-5p ratio was significantly higher in patients with prostate cancer than in healthy controls (p<0.001). We found that exosomal miR-141-5p in plasma showed a promise in distinguishing prostate cancer patients with the AUC of 0.652, and for miR-125a-5p, the AUC was 0.691. For the miR-125a-5p/miR-141-5p ratio, the AUC value was 0.793. We found that miR-125a-5p has a weak positive correlation with PSA (correlation coefficient = 0.3413). Moreover, miR-141-5p has been found to hold a negatively no-significant correlation with PSA, with the correlation coefficient is -0.1102. We speculate that, as diagnostic markers for prostate cancer, miR-125-5p and miR-141-5p might be independent of the PSA. In summary, the results of this study suggest that high plasma exosomal expression of miR-141-3p and low expression of miR-125a-5p in plasma exosomes from prostate cancer patients might be useful markers of specific tumor traits associated with prostate cancer. Moreover, the miR-125a-5p/miR-141-5p ratio seems to perform better than either of the single values alone.

MicroRNA-124 inhibits macrophage cell apoptosis via targeting p38/MAPK signaling pathway in atherosclerosis development.

The objective of this study is to characterize the function of microRNA (miR)-124 in the process of coronary artery disease (CAD). Eighty patients, including 40 CAD patients and 40 non-CAD control patients were enrolled in this study. Atherosclerosis model was established in vivo in ApoE-/- mice and in vitro in RAW264.7 cells. Expression of miR-124 and p38 in patients, animal models and cell models were measured by qRT-PCR, western blot and immunohistochemistry assay. Overexpression or suppression of miR-124 was introduced in vitro and in vivo and the expression levels of p38, miR-124, pro- and anti-inflammatory cytokines, and pro- and anti-apoptotic factors were examined. Results showed that miR-124 was decreased, while p38 was increased in CAD patients and atherosclerosis models compared with control group. MiR-124 could target p38 by binding its 3’ untranslated region and negatively regulated the protein expression of p38. Overexpression of miR-124 increased the expression of anti-inflammatory cytokines, reduced the expression of pro- inflammatory cytokines, and inhibited macrophage apoptosis. MiR-124 overexpression may be a promising treatment for atherosclerosis and CAD via inhibiting p38.

A systems approach delivers a functional microRNA catalog and expanded targets for seizure suppression in temporal lobe epilepsy

Temporal lobe epilepsy is the most common drug-resistant form of epilepsy in adults. The reorganization of neural networks and the gene expression landscape underlying pathophysiologic network behavior in brain structures such as the hippocampus has been suggested to be controlled, in part, by microRNAs. To systematically assess their significance, we sequenced Argonaute-loaded microRNAs to define functionally engaged microRNAs in the hippocampus of three different animal models in two species and at six time points between the initial precipitating insult through to the establishment of chronic epilepsy. We then selected commonly up-regulated microRNAs for a functional in vivo therapeutic screen using oligonucleotide inhibitors. Argonaute sequencing generated 1.44 billion small RNA reads of which up to 82% were microRNAs, with over 400 unique microRNAs detected per model. Approximately half of the detected microRNAs were dysregulated in each epilepsy model. We prioritized commonly up-regulated microRNAs that were fully conserved in humans and designed custom antisense oligonucleotides for these candidate targets. Antiseizure phenotypes were observed upon knockdown of miR-10a-5p, miR-21a-5p, and miR-142a-5p and electrophysiological analyses indicated broad safety of this approach. Combined inhibition of these three microRNAs reduced spontaneous seizures in epileptic mice. Proteomic data, RNA sequencing, and pathway analysis on predicted and validated targets of these microRNAs implicated derepressed TGF-β signaling as a shared seizure-modifying mechanism. Correspondingly, inhibition of TGF-β signaling occluded the antiseizure effects of the antagomirs. Together, these results identify shared, dysregulated, and functionally active microRNAs during the pathogenesis of epilepsy which represent therapeutic antiseizure targets.

Long non-coding RNAs and TGF-β signaling in cancer.

Cancer is driven by genetic mutations in oncogenes and tumor suppressor genes and by cellular events that develop a misregulated molecular microenvironment in the growing tumor tissue. The tumor microenvironment is guided by the excessive action of specific cytokines including transforming growth factor‐β (TGF‐β), which normally controls embryonic development and the homeostasis of young or adult tissues. As a consequence of the genetic alterations generating a given tumor, TGF‐β can preserve its homeostatic function and attempt to limit neoplastic expansion, whereas, once the tumor has progressed to an aggressive stage, TGF‐β can synergize with various oncogenic stimuli to facilitate tumor invasiveness and metastasis. TGF‐β signaling mechanisms via Smad proteins, various ubiquitin ligases, and protein kinases are relatively well understood. Such mechanisms regulate the expression of genes encoding proteins or non‐coding RNAs. Among non‐coding RNAs, much has been understood regarding the regulation and function of microRNAs, whereas the role of long non‐coding RNAs is still emerging. This article emphasizes TGF‐β signaling mechanisms leading to the regulation of non‐coding genes, the function of such non‐coding RNAs as regulators of TGF‐β signaling, and the contribution of these mechanisms in specific hallmarks of cancer.

Strategies to Modulate MicroRNA Functions for the Treatment of Cancer or Organ Injury.

Cancer and organ injury-such as that occurring in the perioperative period, including acute lung injury, myocardial infarction, and acute gut injury-are among the leading causes of death in the United States and impose a significant impact on quality of life. MicroRNAs (miRNAs) have been studied extensively during the last two decades for their role as regulators of gene expression, their translational application as diagnostic markers, and their potential as therapeutic targets for disease treatment. Despite promising preclinical outcomes implicating miRNA targets in disease treatment, only a few miRNAs have reached clinical trials. This likely relates to difficulties in the delivery of miRNA drugs to their targets to achieve efficient inhibition or overexpression. Therefore, understanding how to efficiently deliver miRNAs into diseased tissues and specific cell types in patients is critical. This review summarizes current knowledge on various approaches to deliver therapeutic miRNAs or miRNA inhibitors and highlights current progress in miRNA-based disease therapy that has reached clinical trials. Based on ongoing advances in miRNA delivery, we believe that additional therapeutic approaches to modulate miRNA function will soon enter routine medical treatment of human disease, particularly for cancer or perioperative organ injury. SIGNIFICANCE STATEMENT: MicroRNAs have been studied extensively during the last two decades in cancer and organ injury, including acute lung injury, myocardial infarction, and acute gut injury, for their regulation of gene expression, application as diagnostic markers, and therapeutic potentials. In this review, we specifically emphasize the pros and cons of different delivery approaches to modulate microRNAs, as well as the most recent exciting progress in the field of therapeutic targeting of microRNAs for disease treatment in patients.

Progress of Mesenchymal Stem Cell-Derived Exosomes in Tissue Repair.

Mesenchymal stem cells (MSCs) are a kind of adult stem cells with self-replication and multidirectional differentiation, which can differentiate into tissue-specific cells under physiological conditions, maintaining tissue self-renewal and physiological functions. They play a role in the pathological condition by lateral differentiation into tissue-specific cells, replacing damaged tissue cells by playing the role of a regenerative medicine , or repairing damaged tissues through angiogenesis, thereby, regulating immune responses, inflammatory responses, and inhibiting apoptosis. It has become an important seed cell for tissue repair and organ reconstruction, and cell therapy based on MSCs has been widely used clinically. The study found that the probability of stem cells migrating to the damaged area after transplantation or differentiating into damaged cells is very low, so the researchers believe the leading role of stem cell transplantation for tissue repair is paracrine secretion, secreting growth factors, cytokines or other components. Exosomes are biologically active small vesicles secreted by MSCs. Recent studies have shown that they can transfer functional proteins, RNA, microRNAs, and lncRNAs between cells, and greatly reduce the immune response. Under the premise of promoting proliferation and inhibition of apoptosis, they play a repair role in tissue damage, which is caused by a variety of diseases. In this paper, the biological characteristics of exosomes (MSCs-exosomes) derived from mesenchymal stem cells, intercellular transport mechanisms, and their research progress in the field of stem cell therapy are reviewed.

MicroRNA hsa-miR-1301-3p Regulates Human ADH6, ALDH5A1 and ALDH8A1 in the Ethanol-Acetaldehyde-Acetate Metabolic Pathway

Alcohol dehydrogenases (ADHs) and aldehyde dehydrogenases (ALDHs) are vital enzymes involved in the metabolism of a variety of alcohols. Differences in the expression and enzymatic activity of human ADHs and ALDHs correlate with individual variability in metabolizing alcohols and drugs and in the susceptibility to alcoholic liver disease. MicroRNAs (miRNAs) function as epigenetic modulators to regulate the expression of drug-metabolizing enzymes. To characterize miRNAs that target ADHs and ALDHs in human liver cells, we carried out a systematic bioinformatics analysis to analyze free energies of the interaction between miRNAs and their cognate sequences in ADH and ALDH transcripts and then calculated expression correlations between miRNAs and their targeting ADH and ALDH genes using a public data base. Candidate miRNAs were selected to evaluate bioinformatic predictions using a series of biochemical assays. Our results showed that 11 miRNAs have the potential to modulate the expression of two ADH and seven ALDH genes in the human liver. We found that hsa-miR-1301-3p suppressed the expression of ADH6, ALDH5A1, and ALDH8A1 in liver cells and blocked their induction by ethanol. In summary, our results revealed that hsa-miR-1301-3p plays an important role in ethanol metabolism by regulating ADH and ALDH gene expression. SIGNIFICANCE STATEMENT: Systematic bioinformatics analysis showed that 11 microRNAs might play regulatory roles in the expression of two alcohol dehydrogenase (ADH) and seven aldehyde dehydrogenase (ALDH) genes in the human liver. Experimental evidences proved that hsa-miR-1301-3p suppressed the expression of ADH6, ALDH5A1, and ALDH8A1 in liver cells and decreased their inducibility by ethanol.

MiRNet 2.0: network-based visual analytics for miRNA functional analysis and systems biology

miRNet is an easy-to-use, web-based platform designed to help elucidate microRNA (miRNA) functions by integrating users' data with existing knowledge via network-based visual analytics. Since its first release in 2016, miRNet has been accessed by >20 000 researchers worldwide, with ∼100 users on a daily basis. While version 1.0 was focused primarily on miRNA-target gene interactions, it has become clear that in order to obtain a global view of miRNA functions, it is necessary to bring other important players into the context during analysis. Driven by this concept, in miRNet version 2.0, we have (i) added support for transcription factors (TFs) and single nucleotide polymorphisms (SNPs) that affect miRNAs, miRNA-binding sites or target genes, whilst also greatly increased (>5-fold) the underlying knowledgebases of miRNAs, ncRNAs and disease associations; (ii) implemented new functions to allow creation and visual exploration of multipartite networks, with enhanced support for in situ functional analysis and (iii) revamped the web interface, optimized the workflow, and introduced microservices and web application programming interface (API) to sustain high-performance, real-time data analysis. The underlying R package is also released in tandem with version 2.0 to allow more flexible data analysis for R programmers. The miRNet 2.0 website is freely available at https://www.mirnet.ca.

MiR-301a Promotes Cell Proliferation by Repressing PTEN in Renal Cell Carcinoma.

ObjectiveRenal cell carcinoma (RCC) displays an increasing incidence and mortality rate worldwide in recent years. More and more evidence demonstrated microRNAs function as positive or negative regulatory factors in many cancers, while the role of miR-301a in RCC is still unclear.Material and MethodsThe expression and clinical significance of miR-301a were assessed via bioinformatic software on open microarray datasets of the Cancer Genome Atlas (TCGA) and then confirmed by quantitative real-time PCR (qRT-PCR) in RCC cell lines. Loss of function assays were performed in RCC cell lines both in vitro and in vivo. Cell Counting Kit-8 (CCK-8), flow cytometry, luciferase reporter assays, Western blotting, and immunohistochemistry were employed to explore the mechanisms of the effect of miR-301a on RCC.ResultsBy analyzing RCC clinical specimens and cell lines, we found a uniform increased miR-301a in expression in comparison with normal renal tissue or normal human proximal tubule epithelial cell line (HK-2). In addition, miR-301a upregulation correlated advanced stage and poor prognosis of clear cell RCC (ccRCC). Anti-miR-301a could inhibit growth and cell cycle G1/S transition in RCC cell lines. Moreover, we found that PTEN was identified as a direct target of miR-301a that might partially interrupt miR-301a-induced G1/S transition. Importantly, nude-mouse models revealed that knockdown of miR-301a delayed tumor growth.ConclusionThese results indicate that miR-301a functions as a tumor-promoting miRNA through regulating PTEN expression, representing a novel therapeutic target for RCC.

Tumor suppressor role of miR-876-5p in gastric cancer.

Gastric cancer (GC) is the second most common cancer cause of cancer-related mortality worldwide. Recent studies have demonstrated the function of microRNAs (miRNAs) in the pathogenesis of GC. miR-876-5p demonstrated an antitumor role in hepatocellular carcinoma and lung cancer; however, the function of miR-876-5p has not yet been fully identified in GC. Thus, the present study aimed to investigate the role of miR-876-5p in GC. The results of the present study demonstrated low expression levels of miR-876-5p in GC tumor tissues. Furthermore, overexpression of miR-876-5p inhibited GC cell proliferation and promoted apoptosis, whilst miR-876-5p knockdown promoted GC cell proliferation and decreased cisplatin sensitivity of GC cells. Transforming growth factor β-receptor 1 was demonstrated to be a potential target gene of miR-876-5p. Overall, the results of the present study suggest that miR-876-5p plays an antitumor role in GC.

MiR‑29b promotes the osteogenic differentiation of mesenchymal stem cells derived from human adiposetissue via the PTEN/AKT/β‑catenin signaling pathway.

Accumulating evidence has documented that microRNAs (miRNAs or miRs) function as important post-transcriptional regulators of the differentiation of mesenchymal stem cells (MSCs), including human adipose-derived mesenchymal stem cells (hADSCs); however, their roles in hADSC osteogenic differentiation require further investigation. The present study aimed to investigate the role of miRNAs in the osteogenic differentiation of hADSCs and to elucidate the underlying molecular mechanisms. Using an miRNA microarray, it was found that 24 miRNAs were upregulated and 14 miRNAs were downregulated compared with the undifferentiated cells, and miR-29b-3p (miR-29b) was selected for further experiments. Functional experiments revealed that the upregulation of miR-29b by agomir-29b significantly enhanced alkaline phosphatase (ALP) activity and the mineralization of extracellular matrix (ECM), and led to an increase in the mRNA and protein levels of osteogenic marker genes, including runt-related transcription factor 2 (Runx2), osteopontin (OPN), osteocalcin (OCN) and bone sialoprotein (BSP), whereas the knockdown of miR-29b suppressed these processes. In addition, phosphatase and tensin homolog (PTEN), a negative regulator of the AKT/β-catenin pathway, was identified as a direct target of miR-29b in the hADSCs. Moreover, it was observed that the overexpression of miR-29b activated the AKT/β-catenin signaling pathway by inhibiting PTEN expression in the hADSCs. Most importantly, it was also found that the overexpression of PTEN reversed the promoting effects of miR-29b on osteogenic differentiation. On the whole, these findings suggest that miR-29b promotes the osteogenic differentiation of hADSCs by modulating the PTEN/AKT/β-catenin signaling pathway. Thus, this miRNA may be a promising target for the active modulation of hADSC-derived osteogenesis.

Exosomal microRNA in serum is a prognostic factor in cutaneous squamous cell carcinoma.

e22073 Background: Functional microRNA(miRNAs) is located in the area of the gene related to cancer, such as inside of oncogenes and tumor suppressor genes, loss of heterozygocity or fragile site. There are many studies show that abnormal increase expression of miRNAs when cancer occurs. While some miRNAs commonly suppress abnormal expression of tumors, they can also infer the orgin of tumor tissues because they are more often representative of unique miRNA depending on type of tumor. In many case, the miRNAs expression patterns provide more characteristic information about tumors than messenger RNA expression profinling. The miRNAs expression patterns, which have changed with tumor types, provide clue that can serve as a biological markers for diagnosis, determining the outcome of disease, and predicting treatment responses. Indeed, several studies have reported thatextracellular miRNA is related to the prognosis of disease in some cancers, such as colon cancer and breast cancer. However, so far, there is no study that has been no defenitive study on how exosomal miRNAsare related to progrosis in cutaneous squamous cell carcinoma. We studied the association between the patient’s prognosis and miRNAs detected in cancer tissue and blood serum. Methods: We analyzed 35 patients who have various stage of cutaneous squamous cell carcinoma. Cancer tissue and serum samples were sequentially obtained. The miRNAs were prified from serum exosome and cancer tissues, and miRNAs sequencing was performed. The miRNAs expression profiles and copy number variations were observed using next generation sequencing (Hiseq, illumina inc) in 35 cancer tissues and serum samples. We validated miRNAs change and patient’s prognosis. Results: miR-142-5p cluster expression level in serum exosome and cancer tissue was most correlated with poor prognosis of cutaneous squamous cell carcinoma. Exosomal miR-142-5p expression level in serum were significantly higher(P &lt; 0.01) in patients with late stage than in patients with early stage. Also, the patients with recurrence showed high level of miR-142-5p. Conclusions: miR-142-5p expression level may be an important marker for predicting the patient’s prognosis and deciding whether undergo additional systemic chemotherapy after surgery.

Relationship between Sphk1/S1P and microRNAs in human cancers.

Sphingosine kinases type 1 (SphK1) is a key enzyme in the phosphorylation of sphingosine to sphingosine 1-phosphate (S1P). Different abnormalities in SphK1 functions may correspond with poor prognosis in various cancers. Additionally, upregulated SphK1/S1P could promote cancer cell proliferation, angiogenesis, mobility, invasion, and metastasis. MicroRNAs as conserved small noncoding RNAs play major roles in cancer initiation, progression, metastasis, etc. Their posttranscriptionally mechanisms could affect the development of cancer growth or tumorigenesis suppression. The growing number of studies has described that various microRNAs can be regulated by SphK1, and its expression level can also be regulated by microRNAs. In this review, the relationship of SphK1 and microRNA functions and their interaction in human malignancies have been discussed. Based on them novel treatment strategies can be introduced.

Epigenetic Mechanisms in Nematode-Plant Interactions.

Epigenetic mechanisms play fundamental roles in regulating numerous biological processes in various developmental and environmental contexts. Three highly interconnected epigenetic control mechanisms, including small noncoding RNAs, DNA methylation, and histone modifications, contribute to the establishment of plant epigenetic profiles. During the past decade, a growing body of experimental work has revealed the intricate, diverse, and dynamic roles that epigenetic modifications play in plant-nematode interactions. In this review, I summarize recent progress regarding the functions of small RNAs in mediating plant responses to infection by cyst and root-knot nematodes, with a focus on the functions of microRNAs. I also recapitulate recent advances in genome-wide DNA methylation analysis and discuss how cyst nematodes induce extensive and dynamic changes in the plant methylome that impact the transcriptional activity of genes and transposable elements. Finally, the potential role of nematode effector proteins in triggering such epigenome changes is discussed.