Biological Functions of Autophagy Genes: A Disease Perspective

https://www.cell.com/article/S0092867419305549/pdf

Autophagy-Independent Functions of the Autophagy Machinery

Epidemiology of colorectal cancer

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

Guidelines for the use and interpretatoin of assays for monitoring autophagy

Structural Basis for Target-Directed MicroRNA Degradation.

http://tsp.techscience.com//uploads/attached/file/20181009/20181009072959_55692.pdf

Kaempferol and docetaxel diminish side population and down-regulate some cancer stem cell markers in breast cancer cell line MCF-7

Long non-coding RNAs (lncRNAs) have a critical role in the regulation of cardiovascular function. Dysregulation of lncRNAs is implicated in the progression of cardiovascular diseases including myocardial infarction (MI). Regarding the beneficial effects of exercise (Ex) on the improvement of MI, this study aimed to investigate the effects of post-MI Ex on the expression of MI-associated lncRNAs: H19, myocardial infarction association transcript (MIAT), and growth arrest specific 5 (GAS5). MI was induced by left anterior descending (LAD) coronary artery ligation in male Wistar rats. One week later, rats were exercised under a moderate-intensity protocol for 4 weeks. In the end, hemodynamic parameters and cardiac function indices were measured. Assessment of fibrotic areas and apoptosis was performed by Masson's trichrome staining and immunohistochemistry, respectively. Expression of genes was evaluated by real-time PCR. Ex significantly reduced the fibrotic areas (P < 0.05) and apoptosis and increased contractility indices (P < 0.01), and cardiac function (P < 0.05) in MI groups. The reduced expression of H19 (P < 0.01) in MI rats returned to normal levels by Ex. Ex significantly (P < 0.001) reduced the expression of MIAT and increased the expression of GAS5 (P < 0.01), which had changed in the hearts of rats with MI. The present study indicated the beneficial effect of Ex on the improvement of cardiac function and reduction of fibrosis in infarcted heart possibly through regulation of the expression of lncRNAs: H19, GAS5, and MIAT.

Modulation of the Expression of Long Non-Coding RNAs H19, GAS5, and MIAT by Endurance Exercise in the Hearts of Rats with Myocardial Infarction

Lung cancer is the most common cause of cancer-related deaths worldwide. Annually, millions of people die from lung cancer because of late detection and ineffective therapies. Recently, exosomes have been introduced as new therapeutic players with the potential to improve upon current diagnostic and treatment options. Exosomes are small membranous vesicles produced during endosomal merging. This allows for cell packaging of nucleic acids, proteins, and lipids and transfer to adjacent or distant cells. While exosomes are a part of normal intercellular signaling, they also allow malignant cells to transfer oncogenic material leading to tumor spread and metastasis. Exosomes are an interesting field of discovery for biomarkers and therapeutic targets. Among exosomal materials, lncRNAs have priority; lncRNAs are a class of noncoding RNAs longer than 200 base pairs. In the case of cancer, primary interest regards their oncogene and tumor suppressor functions. In this review, the advantages of exosomal lncRNAs as biomarkers and therapeutic targets will be discussed in addition to reviewing studies of their application in lung cancer.

/pdf/exosomal-long-noncoding-rnas-insights-into-emerging-4rbb6bc7ho.pdf

Exosomal Long Noncoding RNAs: Insights into Emerging Diagnostic and Therapeutic Applications in Lung Cancer.

There is a high level of heterogeneity in symptom manifestations and response to disease-modifying therapies (DMTs) in multiple sclerosis (MS), an immune-based neurodegenerative disease with ever-increasing prevalence in recent decades Because of unknown aspects of the etiopathology of MS and mechanism of action of DMTs, the reason for this variability is undetermined, and much remains to be understood Traditionally, physicians consider switching to other DMTs based on the exacerbation of symptoms and/or change in the results of magnetic resonance imaging and biochemical factors Therefore, identifying biological treatment response markers that help us recognizing non-responders rapidly and subsequently choosing another DMTs is necessary microRNAs (miRNAs) are micromanagers of gene expression which have been profiled in different samples of MS patients, highlighting their role in pathogenetic of MS Recent studies have investigated expression profiling of miRNAs after treatment with DMTs to clarify possible DMTs-mediated mechanism and obtaining response to therapy biomarkers In this review, we will discuss the modulation of miRNAs by DMTs in cells and pathways involved in MS

Mohammad Reza Karimzadeh

Papers

Kaempferol and docetaxel diminish side population and down-regulate some cancer stem cell markers in breast cancer cell line MCF-7

Modulation of the Expression of Long Non-Coding RNAs H19, GAS5, and MIAT by Endurance Exercise in the Hearts of Rats with Myocardial Infarction

Exosomal Long Noncoding RNAs: Insights into Emerging Diagnostic and Therapeutic Applications in Lung Cancer.

microRNAs: key modulators of disease-modifying therapies in multiple sclerosis.

Alterations of epigenetic landscape in Down syndrome carrying pregnancies: A systematic review of case-control studies.