Acute myocardial infarction (AMI), as the first manifestation of ischemic heart disease, is the most common cause of death in developed countries. A recent study showed that metastasis associated lung adenocarcinoma transcript 1 (MALAT1), a prognostic marker for lung cancer metastasis, could promote myocardial ischemia-reperfusion injury by regulating the levels of microRNA (miR)-145. In order to elucidate the biological function of MALAT1 in the pathogenesis of AMI and to explore the mechanisms underlying its action, an AMI rat model was established by ligation of the left anterior descending coronary artery. Downregulation of MALAT1 by siRNA transfection attenuated heart damage in an AMI model rat. The mouse cardiomyocyte cell line HL-1 was used to show that downregulation of nucleotide binding and oligomerization domain-like receptor C5 (NLRC5) and upregulation of miR-125b-5p were the results of MALAT1 silencing. TargetScan and a dual-luciferase reporter assay indicated that NLRC5 is a direct target of miR-125b-5p. Overexpression of miR-125b-5p significantly reduced hypoxia/reperfusion-induced apoptosis of HL-1 cells, an effect that could be blocked by NLCR5 overexpression. Taken together, these results suggest that MALAT1 reduced the protective effect of miR-125b-5p on injured cells through upregulation of NLCR5. This study highlights the role of MALAT1 in the pathogenesis of AMI and may guide future genetic therapeutic strategies for AMI treatment.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Since most patients with HCC are diagnosed at the intermediate or advanced stage and because HCC has a high incidence of metastasis and recurrence, it is one of the leading causes of cancer death. Exosomes are a subtype of extracellular vesicles and are typically 30–150 nm in diameter. Originating from endosomes, they can be secreted by almost all living cells. They are widely present in various body fluids and serve as an important medium for the interactions between cells. A series of studies have revealed that exosomes-mediated intercellular transfer of proteins, nucleic acids, and metabolites plays a crucial role in the initiation and progression of HCC, hypoxia and angiogenesis, chemotherapy sensitivity, and cell death mode and regulates the immune microenvironment. In this paper, we reviewed the recent researches on the multiple roles of tumor-associated exosomes in the progression of HCC. We laid particular focus on those researches that reveal how exosomes regulate the tumor immune microenvironment (TIME) and how exosomal cargos affect the progression of HCC. Besides, we emphasize some prospective directions to achieve a more accurate and complete analysis of the HCC immune microenvironment.

Autophagy has been shown to maintain neural system homeostasis during stroke. However, the molecular mechanisms underlying neuronal autophagy in ischemic stroke remain poorly understood. This study aims to investigate the regulatory mechanisms of the pathway consisting of maternally expressed gene 3 (MEG3), microRNA-378 (miR-378), and growth factor receptor-bound protein 2 (GRB2) in neuronal autophagy and neurological functional impairment in ischemic stroke. A mouse model of the middle cerebral artery occluded (MCAO)-induced ischemic stroke and an in vitro model of oxygen-glucose deprivation (OGD)-induced neuronal injury were developed. To understand the role of the MEG3/miR-378/GRB2 axis in the neuronal regulation, the expression of proteins associated with autophagy in neurons was measured by Western blot analysis and neuron death was evaluated using LDH leakage rate test. Firstly, it was found that the GRB2 gene, up-regulated in MCAO-operated mice and OGD-exposed neurons, was a target gene of miR-378. Next, miR-378 inhibited neuronal loss and neurological functional impairment in mice as well as neuronal autophagy and neuronal death by silencing of GRB2. Confirmatory in vitro experiments showed that MEG3 could specifically bind to miR-378 and subsequently up-regulate the expression of GRB2, which in turn suppressed the activation of Akt/mTOR pathway. Taken together, these findings suggested that miR-378 might protect against neuronal autophagy and neurological functional impairment, and proposed that a MEG3/miR-378/GRB2 regulatory axis contributed to better understanding of the pathophysiology of ischemic stroke.

Fatty liver disease (FLD) is a growing health issue with burdening unmet clinical needs. FLD has a genetic component but, despite the common variants already identified, there is still a missing heritability component. Using a candidate gene approach, we identify a locus (rs71519934) at the Pleckstrin and Sec7 domain-containing 3 (PSD3) gene resulting in a leucine to threonine substitution at position 186 of the protein (L186T) that reduces susceptibility to the entire spectrum of FLD in individuals at risk. PSD3 downregulation by short interfering RNA reduces intracellular lipid content in primary human hepatocytes cultured in two and three dimensions, and in human and rodent hepatoma cells. Consistent with this, Psd3 downregulation by antisense oligonucleotides in vivo protects against FLD in mice fed a non-alcoholic steatohepatitis-inducing diet. Thus, translating these results to humans, PSD3 downregulation might be a future therapeutic option for treating FLD.

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