LncRNA SETD5-AS1 is Upregulated in the Plasma of Ischemic Stroke Patients and Inhibits Cell Proliferation through the PI3K-AKT Pathway

LI Haipeng^1,2, LIU Yifan^1,2, FAN Huihui^1,2, LEI Jinglin^1,2, HU Zheng^1,3*

(¹Translational Medicine Institute, the First People’s Hospital of Chenzhou, Hengyang Medical School, University of South China, Chenzhou 423000, China; ²Department of Neurology, the First People’s Hospital of Chenzhou, the First Clinical College, University of Xiangnan, Chenzhou 423000, China; ³Translational Medicine Institute, the First People’s Hospital of Chenzhou, the First Clinical College, University of Xiangnan, Chenzhou 423000, China)

Abstract:

This study was to investigate the expression of long non-coding RNA SETD5-AS1 in plasma from IS (ischemic stroke) patients and its effects on IS cells, dynamic analysis of plasma transcriptome by sequencing was performed to investigate changes in plasma lncRNA expression in three high-risk individuals before and after the onset of stroke. The lncRNA SETD5-AS1 was identified as significantly upregulated in post-stroke plasma of IS patients. In an OGD/R (oxygen-glucose deprivation/reoxygenation) cell model, the effects of overexpression and knockdown of SETD5-AS1 on the viability and proliferation of SH-SY5Y cells were assessed using CCK-8 and EDU assays. KEGG pathway analysis was conducted to identify key signaling pathways associated with differentially expressed lncRNAs. Western blot was employed to examine the protein levels and phosphorylation status of the AKT and PI3K. Furthermore, plasma samples from 54 high-risk IS individuals and 56 stroke patients within 24 h of onset were collected, and RT-qPCR was performed to detect SETD5-AS1 expression. ROC (receiver operating characteristic) curve analysis was carried out to evaluate its early diagnostic value. Additionally, validation of this lncRNA expression was conducted in 16 patients with paired plasma samples collected before and after stroke onset. The results of this study found the expression of SETD5-AS1 showed the most significant difference before and after the onset of IS in three patients. Overexpression of lncRNA SETD5-AS1 reduced cell viability, prolifera- tion capacity, and the expression of p-AKT and p-PI3K protein phosphorylation levels following OGD/R; while knockdown of lncRNA SETD5-AS1 resulted in the opposite effects. In the plasma of IS patients, SETD5-AS1 expression was significantly upregulated after onset compared to before onset. ROC curve analysis indicated that SETD5-AS1 possesses favorable diagnostic and predictive value. This study demonstrates lncRNA SETD5-AS1 of IS plasma is markedly up-regulated after IS onset and contributes to the pathogenesis of IS by inhibiting cell proliferation through blocking the PI3K-AKT signaling pathway, indicating its potential clinical value in early warning and diagnosis for IS.

CSTR: 32200.14.cjcb.2026.04.0008