Protective effect of microRNA-138 against cerebral ischemia/reperfusion injury in rats

Abstract

Abstract. MicroRNAs (miRs) serve a regulatory function in oxidative radical-mediated inflammation and apoptosis during ischemia/reperfusion (IR) injury. Lipocalin 2 (Lcn-2), a target protein of miR-138, is widely involved in the systemic response to IR injury. The aim of the present study was to investigate the association between miR-138 and Lcn-2 in a rat model of cerebral ischemia/reperfusion (CIR) injury and to verify the interaction between miR-138 and Lcn-2 in a PC12 cell model of hypoxia/reoxygenation injury. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to detect the mRNA and protein expression levels of miR-138 and Lcn-2. Cell proliferation was determined by MTT assay. The results suggested that the expression of miR-138 was inversely correlated with the expression of Lcn-2 in the CIR rat model and the PC12 cells subjected to hypoxia and reoxygenation. The expression of Lcn-2 was inhibited by miR-138 mimics and enhanced by miR-138 inhibitors, thereby indicating that miR-138 functions as a negative regulator for Lcn-2 expression. This study provides an experimental basis for the further study of miR-138-based therapy for CIR injury.

Retracted: Protective effects of microRNA‐431 against cerebral ischemia‐reperfusion injury in rats by targeting the Rho/Rho‐kinase signaling pathway

“…This was similar to the findings of Pan et al that miR‐431 was down‐regulated in samples with hepatocellular carcinoma and that down‐regulation of miR‐431 partially contributed to hepatocellular carcinoma progression (Pan et al, ). Growing studies have found that miRNAs regulate cell activities in cerebral ischemia‐reperfusion injury, for instance, miR‐138 played protective roles against cerebral ischemia‐reperfusion injury by negatively regulating Lcn‐2 (Di et al, ; Tang et al, ). The down‐regulation of miR‐30a alleviated ischemic injury through enhancing beclin 1‐mediated autophagy (Wang et al, ).…”

“…Cerebral ischemia‐reperfusion injury is defined as a permanent or transient cerebral blood flow reduction or pause that impedes the central nervous system to meet the functional or metabolic demand (Yu et al, ). It occurred when blood vessel was blocked and further exacerbated by sudden recovery of the blood supply, causing the dysfunction of neurons, glia cells, and cerebral blood vessels (Ioroi et al, ; Tang et al, ). Cerebral ischemia‐reperfusion injury‐induced ischemic stroke has been reported to become the third leading cause of death, only after heart disease and cancer (Liang, Shi, Luo, & Yang, ).…”

MicroRNA-138-5p targets pro-apoptotic factors and favours neural cell survival

“…(but also HIF-1α [65,66])-contribute to the cell death processes of secondary injury [67,68], suggesting that miR-138-5p can be considered a cytoprotectant whose downregulation contributes to extend neural cell death after SCI, as described by Tang and colleagues [63] for cerebral ischemia/reperfusion injury. In apparent opposition with this possibility, many cancer researchers consider miR-138-5p a tumour suppressor that becomes downregulated in different cancer processes, such as leukemia [69], lung cancer [70] and hepatocellular carcinoma [71].…”

“…Even though the deleterious effects of miR-138-5p downregulation in the damaged CNS are explored here for the first time, the cytoprotective properties of this miRNA are well documented in astrocytes injured under ischemic conditions [56], glioblastoma [57], glioma stem cells [25], as well as in neural stem cells [58], pulmonary artery smooth muscle cells [59] and cardiomyocytes under hypoxia [60,61], and in microglial cells exposed to oxidative levels of H2O2 [62]. According to these studies, cytoprotection by miR-138-5p relies on its targeting and inhibition of the cell death-related genes Casp3, BLCAP and MXD1 [25], LCN2 [56,63], BIM [57], Mst-1 [64], and Mlk3 [61,62], or even in the inhibition of the JNK and p38MAPK pathways [58]. Some of these targets -including Casp3, Mst-1, BIM, and MLK3…”

Pathophysiology and Clinical Utility of Non-coding RNAs in Epilepsy

“…Wang et al ( 2015 ) reported that circular RNA100783 may be involved in chronic CD28-associated CD8 (+) T cell aging and global immunosenescence. miR-138 has a protective effect on brain injury and can regulate T helper 1 (Th1) and T helper 2 (Th2) expressions via inhibiting the function of runt-related transcription factor 3 (RUNX3) and regulate IL-1β through targeting Forkhead Box C1 (Fu et al, 2015 ; Tang et al, 2016 ; Yuan et al, 2016b ). Circular RNA SRY can act as natural miRNA sponges to suppress miR-138 activity (Granados-Riveron and Aquino-Jarquin, 2014 ).…”