Interaction of autophagy with microRNAs and their potential therapeutic implications in human cancers

AbstractAutophagy is a tightly regulated intracellular self-digestive process involving the lysosomal degradation of cytoplasmic organelles and proteins. A number of studies have shown that autophagy is dysregulated in cancer initiation and progression, or cancer cells under various stress conditions. As a catabolic pathway conserved among eukaryotes, autophagy is regulated by the autophagy related genes and pathways. MicroRNAs (miRNAs) are small, non-coding endogenous RNAs that may regulate almost every cellular process including autophagy. And autophagy is also involved in the regulation of miRNAs expression and homeostasis. Here we reviewed some literatures on the interaction of miRNAs with autophagy and the application of miRNAs-mediated autophagic networks as a promising target in pre-clinical cancer models. Furthermore, strategies of miRNAs delivery for miRNAs-based anti-cancer therapy will also be summarized and discussed

Loss of Abhd5 Promotes Colorectal Tumor Development and Progression by Inducing Aerobic Glycolysis and Epithelial-Mesenchymal Transition

How cancer cells shift metabolism to aerobic glycolysis is largely unknown. Here, we show that deficiency of a/b-hydrolase domain-containing 5 (Abhd5), an intracellular lipolytic activator that is also known as comparative gene identification 58 (CGI-58), promotes this metabolic shift and enhances malignancies of colorectal carcinomas (CRCs). Silencing of Abhd5 in normal fibroblasts induces malignant transformation. Intestine-specific knockout of Abhd5 in ApcMin/+ mice robustly increases tumorigenesis and malignant transformation of adenomatous polyps. In colon cancer cells, Abhd5 deficiency induces epithelial-mesenchymal transition by suppressing the AMPKa-p53 pathway, which is attributable to increased aerobic glycolysis. In human CRCs, Abhd5 expression falls substantially and correlates negatively with malignant features. Our findings link Abhd5 to CRC pathogenesis and suggest that cancer cells develop aerobic glycolysis by suppressin

ALS-Associated E478G Mutation in Human OPTN (Optineurin) Promotes Inflammation and Induces Neuronal Cell Death

Amyotrophic Lateral Sclerosis (ALS) is a group of neurodegenerative disorders that featured with the death of motor neurons, which leads to loss of voluntary control on muscles. The etiologies vary among different subtypes of ALS, and no effective management or medication could be provided to the patients, with the underlying mechanisms incompletely understood yet. Mutations in human Optn (Optineurin), particularly E478G, have been found in many ALS patients. In this work, we report that NF-κB activity was increased in Optn knockout (Optn−/−) MEF (mouse embryonic fibroblast) cells expressing OPTN of different ALS-associated mutants especially E478G. Inflammation was significantly activated in mice infected with lenti-virus that allowed overexpression of OPTNE478G mutation in the motor cortex, with marked increase in the secretion of pro-inflammatory cytokines as well as neuronal cell death. Our work with both cell and animal models strongly suggested that anti-inflammation treatment could represent a powerful strategy to intervene into disease progression in ALS patients who possess the distinctive mutations in OPTN gene

Differential effects of warming on the complexity and stability of the microbial network in Phragmites australis and Spartina alterniflora wetlands in Yancheng, Jiangsu Province, China

The impact of climate warming on soil microbial communities can significantly influence the global carbon cycle. Coastal wetlands, in particular, are susceptible to changes in soil microbial community structure due to climate warming and the presence of invasive plant species. However, there is limited knowledge about how native and invasive plant wetland soil microbes differ in their response to warming. In this study, we investigated the temporal dynamics of soil microbes (prokaryotes and fungi) under experimental warming in two coastal wetlands dominated by native Phragmites australis (P. australis) and invasive Spartina alterniflora (S. alterniflora). Our research indicated that short-term warming had minimal effects on microbial abundance, diversity, and composition. However, it did accelerate the succession of soil microbial communities, with potentially greater impacts on fungi than prokaryotes. Furthermore, in the S. alterniflora wetland, experimental warming notably increased the complexity and connectivity of the microbial networks. While in the P. australis wetland, it decreased these factors. Analysis of robustness showed that experimental warming stabilized the co-occurrence network of the microbial community in the P. australis wetland, but destabilized it in the S. alterniflora wetland. Additionally, the functional prediction analysis using the Faprotax and FunGuild databases revealed that the S. alterniflora wetland had a higher proportion of saprotrophic fungi and prokaryotic OTUs involved in carbon degradation (p < 0.05). With warming treatments, there was an increasing trend in the proportion of prokaryotic OTUs involved in carbon degradation, particularly in the S. alterniflora wetland. Therefore, it is crucial to protect native P. australis wetlands from S. alterniflora invasion to mitigate carbon emissions and preserve the health of coastal wetland ecosystems under future climate warming in China

Anomalous High-Energy Waterfall-Like Electronic Structure in 5 \u3cem\u3ed\u3c/em\u3e Transition Metal Oxide Sr\u3csub\u3e2\u3c/sub\u3eIrO\u3csub\u3e4\u3c/sub\u3e with a Strong Spin-Orbit Coupling

The low energy electronic structure of Sr2IrO4 has been well studied and understood in terms of an effective Jeff = 1/2 Mott insulator model. However, little work has been done in studying its high energy electronic behaviors. Here we report a new observation of the anomalous high energy electronic structure in Sr2IrO4. By taking high-resolution angle-resolved photoemission measurements on Sr2IrO4 over a wide energy range, we have revealed for the first time that the high energy electronic structures show unusual nearly-vertical bands that extend over a large energy range. Such anomalous high energy behaviors resemble the high energy waterfall features observed in the cuprate superconductors. While strong electron correlation plays an important role in producing high energy waterfall features in the cuprate superconductors, the revelation of the high energy anomalies in Sr2IrO4, which exhibits strong spin-orbit coupling and a moderate electron correlation, points to an unknown and novel route in generating exotic electronic excitations