LncRNA ANRIL protects against oxygen and glucose deprivation (OGD)-induced injury in PC-12 cells: potential role in ischaemic stroke

Abstract

lncRNA ANRIL was reported to be closely related to ischaemic stroke (IS). In this study, we used oxygen-glucose deprivation (OGD) to stimulate rat adrenal medulla-derived pheochromocytoma cell line PC-12 to construct an in vitro IS cell model and investigated the role of ANRIL and the underlying mechanism. PC-12 cells were stimulated by OGD and/or transfected with pc-ANRIL, si-ANRIL, miR-127 mimic, miR-127 inhibitor, pEX-Mcl-1, sh-Mcl-1 and their negative controls. Cell viability, apoptosis, mRNA and protein expression was detected using CCK-8 assay, flow cytometry assay, qRT-PCR and western blot, respectively. Results showed that OGD-induced PC-12 cell injury and decreased ANRIL expression. ANRIL overexpression significantly reduced OGD-induced PC-12 cell injury evidenced by increasing cell viability and decreasing apoptosis, while ANRIL silence led to the opposite results. Meanwhile, dysregulation of ANRIL altered the expression of apoptotic proteins. Furthermore, ANRIL negatively regulated miR-127 expression. miR-127 overexpression significantly enhanced OGD-induced PC-12 cell injury. In addition, Mcl-1 expression was negatively regulated by miR-127, besides ANRIL upregulated Mcl-1 expression by down-regulation of miR-127. Mcl-1 overexpression alleviated cell injury and miR-127 silence up-regulated Mcl-1 expression. In conclusion, lncRNA ANRIL alleviated OGDinduced PC-12 cell injury as evidenced. PI3K/AKT pathway might be involved in this regulating progression.

<p>Long Non-Coding RNA SNHG7 Alleviates Oxygen and Glucose Deprivation/Reoxygenation-Induced Neuronal Injury by Modulating miR-9/SIRT1 Axis in PC12 Cells: Potential Role in Ischemic Stroke</p>

“…38 Growing literature has shown that down-regulation of lncRNAs is implicated in the pathological process of IS, such as lncRNA Oprm1, 39 lncRNA ZFAS1 40 and lncRNA ANRIL. 34 Coincident with expression trend of previous studies, we also observed that SNHG7 was down-regulated by MCAO treatment in brain tissues of mice and by OGD/R treatment in PC12 cells, implying that SNHG7 might involve in the pathologies of IS. Besides, numerous studies have revealed the key role of SNHG7 in many diseases.…”

“…A rat adrenal pheochromocytoma cell line PC12 with specific characteristic of neural cells was used in accordance with previous studies. [33][34][35][36] PC12 cells were bought from American Type Culture Collection (ATCC, USA). PC12 cells were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin and incubated at 37°C under a humidified atmosphere with 5% CO 2 .…”

Expression Profile and Potential Functions of Circulating Long Noncoding RNAs in Acute Ischemic Stroke in the Southern Chinese Han Population

“…Moreover, circulating leukocytes exhibit cerebral ischemia-induced changes in the RNA expression profile detectable in circulating blood, as demonstrated in a series of animal models of IS (Tang et al, 2001; Sharp et al, 2011; Dagonnier et al, 2018; Li et al, 2019). Although emerging studies have shown that numerous lncRNAs may be involved in the regulation of IS pathophysiologic processes (Dykstra-Aiello et al, 2016; Wu et al, 2017; Zhang et al, 2018; Liu et al, 2019; Zhu et al, 2019), their roles in the pathological mechanisms, nosogenesis and progression of IS still need to be further clarified (Beermann et al, 2016). In the present study, we used high-throughput sequencing technologies to generate a signature profile of numerous lncRNAs and mRNAs in AIS compared with matched healthy controls, and bioinformatics analysis was performed to analyze the data.…”

“…In recent years, numerous researchers have shown great interest in exploring the association between lncRNA profiles and neurological disorders (Wu et al, 2013; Dykstra-Aiello et al, 2016; He et al, 2018). Importantly, an increasing number of studies have shown that lncRNAs play crucial roles in the pathogenesis of IS (Dykstra-Aiello et al, 2016; Liu et al, 2019). Although the functions of most lncRNAs in neuroprotection and IS remain to be clarified (Dharap et al, 2012), RNA-Seq analyses have indicated that the abnormal expression of lncRNAs is closely associated with IS, and increasing evidence has confirmed that lncRNAs generally contribute to the development and progression of IS as well as to recovery from IS (Bhattarai et al, 2017; Guo et al, 2017; Wang et al, 2017; Zhang et al, 2018; Liu et al, 2019).…”

“…As distinct differences exist between animals and humans, the lncRNA profiles in AIS definitely need to be further investigated, especially among different races. Moreover, current research on this issue has focused on only a small number of lncRNAs, such as MIAT, GAS5, MALAT1, SNHG1 and ANRIL (Guo et al, 2017; Chen et al, 2018; Zhang et al, 2018; Zhu et al, 2018; Liu et al, 2019). Many lncRNAs have not yet been discovered in patients with AIS; more importantly, the functions of most lncRNAs have not yet been clarified (Kopp and Mendell, 2018).…”