MCLPMDA: A novel method for miRNA‐disease association prediction based on matrix completion and label propagation

MiRNAs are a class of small non‐coding RNAs that are involved in the development and progression of various complex diseases. Great efforts have been made to discover potential associations between miRNAs and diseases recently. As experimental methods are in general expensive and time‐consuming, a large number of computational models have been developed to effectively predict reliable disease‐related miRNAs. However, the inherent noise and incompleteness in the existing biological datasets have inevitably limited the prediction accuracy of current computational models. To solve this issue, in this paper, we propose a novel method for miRNA‐disease association prediction based on matrix completion and label propagation. Specifically, our method first reconstructs a new miRNA/disease similarity matrix by matrix completion algorithm based on known experimentally verified miRNA‐disease associations and then utilizes the label propagation algorithm to reliably predict disease‐related miRNAs. As a result, MCLPMDA achieved comparable performance under different evaluation metrics and was capable of discovering greater number of true miRNA‐disease associations. Moreover, case study conducted on Breast Neoplasms further confirmed the prediction reliability of the proposed method. Taken together, the experimental results clearly demonstrated that MCLPMDA can serve as an effective and reliable tool for miRNA‐disease association prediction.     

Reversible HuR‐microRNA binding controls extracellular export of miR‐122 and augments stress response

microRNAs (miRNAs), the tiny but stable regulatory RNAs in metazoan cells, can undergo selective turnover in presence of specific internal and external cues to control cellular response against the changing environment. We have observed reduction in cellular miR‐122 content, due to their accelerated extracellular export in human hepatic cells starved for small metabolites including amino acids. In this context, a new role of human ELAV protein HuR has been identified. HuR, a negative regulator of miRNA function, accelerates extracellular vesicle (EV)‐mediated export of miRNAs in human cells. In stressed cells, HuR replaces miRNPs from target messages and is both necessary and sufficient for the extracellular export of corresponding miRNAs. HuR could reversibly bind miRNAs to replace them from Ago2 and subsequently itself gets freed from bound miRNAs upon ubiquitination. The ubiquitinated form of HuR is predominantly associated with multivesicular bodies (MVB) where HuR‐unbound miRNAs also reside. These MVB‐associated pool of miRNAs get exported out via EVs thereby delimiting cellular miR‐122 level during starvation. Therefore, by modulating extracellular export of miR‐122, HuR could control stress response in starved human hepatic cells.     

On the Activity of Alkaline Phosphatase in Intestinal Mucosa from Casein-fed Rats

A novel optical activity of lutein was studied in dodecyltrimethylammonium bromide (DTAB) solution by the measurement of circular dichroism and absorbance. The surfactant was found to bring about the circular dichroism activity of the lutein below the critical micelle concentration (CMC) in a different way from that by sodium dodecyl sulfate (SDS). This phenomenon was interpreted by the card-pack model of the lutein aggregate in which lutein molecule was slightly shifted each other. The above optical activity abruptly became strong just before the CMC of DTAB. This seems to correspond to the transition from the polymeric aggregate of the lutein to the oligomeric one. Such an optical activity disappeared beyond the CMC on the incorporation of the lutein molecules into the surfactant micelles. The molar binding ratios of DTAB to the lutein were determined to be 130 to 210 on the basis of the lutein concentration dependence of the DTAB concentration showing the arbitrary ellipticity. These ratios were clearly larger than those for SDS. On the other hand, filtration measurement showed that the size of the lutein-DTAB complex was larger than 2 μm in diameter. These phenomena were discussed assuming the possible model of the aggregate as a comparative study of the anionic and cationic surfactants causing the novel optical activity of this aggregate.     

植物miRNA介导磷信号转导的研究进展

MicroRNA（miRNA）是一类新型的调控靶基因表达的小分子RNA,参与调节植物的生长发育和抗逆反应等多种生理过程。近年来,随着miR399调节植物磷平衡分子机制的发现,人们开始广泛关注miRNA在低磷信号转导和磷平衡中的作用。本文基于近几年的研究进展,综述miR399、miR827等磷响应miRNA在低磷信号转导以及调节磷平衡过程中的作用和分子生理机制。     

Tumour‐derived exosomes: Tiny envelopes for big stories

The discovery of exosomes, which are small, 30–100 nm sized extracellular vesicles that are released by virtual all cells, has initiated a rapidly expanding and vibrant research field. Current investigations are mainly directed toward the role of exosomes in intercellular communication and their potential value as biomarkers for a broad set of diseases. By horizontal transfer of molecular information such as micro RNAs, messenger RNAs or proteins, as well as by receptor–cell interactions, exosomes are capable to mediate the reprogramming of surrounding cells. Herein, we review how especially cancer cells take advantage of this mechanism to influence their microenvironment in favour of immune escape, therapy resistance, tumour growth and metastasis. Moreover, we provide a comprehensive microarray analysis (n > 1970) to study the expression patterns of genes known to be intimately involved in exosome biogenesis across 26 different cancer entities and a normal tissue atlas. Consistent with the elevated production of exosomes observed in cancer patient plasma, we found a significant overexpression especially of RAB27A, CHMP4C and SYTL4 in the corresponding cancer entities as compared to matched normal tissues. Finally, we discuss the immune‐modulatory and anti‐tumorigenic functions of exosomes as well as innovative approaches to specifically target the exosomal circuits in experimental cancer therapy.