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.

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Visceral hypersensitivity as a common clinical manifestation of irritable bowel syndrome (IBS) may contribute to the development of chronic visceral pain. Our prior studies authenticated that the activation of the corticotropin-releasing factor (CRF) neurons in paraventricular nucleus (PVN) contributed to visceral hypersensitivity in mice, but puzzles still remain with respect to the underlying hyperactivation of corticotropin-releasing factor neurons. Herein, we employed maternal separation (MS) to establish mouse model of visceral hypersensitivity. The neuronal circuits associated with nociceptive hypersensitivity involved paraventricular nucleus CRF neurons by means of techniques such as behavioral test, pharmacology, molecular biology, retrograde neuronal circuit tracers, electrophysiology, chemogenetics and optogenetics. MS could predispose the elevated firing frequency of CRF neurons in PVN in murine adulthood, which could be annulled via the injection of exogenous GABA (0.3mM, 0.2µl) into PVN. The PVN-projecting GABAergic neurons were mainly distributed in the anterior ventral (AV) region in the bed nucleus of stria terminalis (BNST), wherein the excitability of these GABAergic neurons was reduced. Casp3 virus was utilized to induce apoptosis of GABA neurons in BNST-AV region, resulting in the activation of CRF neurons in PVN and visceral hyperalgesia. In parallel, chemogenetic and optogenetic approaches to activate GABAergic BNSTAV-PVN circuit in MS mice abated the spontaneous firing frequency of PVN CRF neurons and prevented the development of visceral hypersensitivity. A priori, PVNCRF-projecting GABAergic neurons in BNST-AV region participated in the occurrence of visceral hypersensitivity induced by MS. Our research may provide a new insight into the neural circuit mechanism of chronic visceral pain.