CircRNA_102046 Affects the Occurrence and Development of Ischemic Stroke by Regulating the miR-493-5p/ROCK1 Signaling

作者全名："He, Wentao; Cheng, Yuanyuan; Lai, Yujie"

作者地址："[He, Wentao; Cheng, Yuanyuan] Chongqing Med Univ, Dept Gen Med, Affiliated Hosp 3, Chongqing 401120, Peoples R China; [Lai, Yujie] Chongqing Med Univ, Dept Neurol, Affiliated Hosp 3, Chongqing 401120, Peoples R China"

通信作者："Cheng, YY (通讯作者)，Chongqing Med Univ, Dept Gen Med, Affiliated Hosp 3, Chongqing 401120, Peoples R China."

来源：CARDIOVASCULAR TOXICOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001168185700002

JCR分区：Q2

影响因子：3.4

年份：2024

卷号：24

期号：3

开始页：280

结束页：290

文献类型：Article

关键词：Ischemic Stroke; CircRNA_102046; miR-493-5p; ROCK1; Human neural stem cells

摘要："In our previous studies, the results have revealed that circRNA_102046 is significantly upregulated in plasma of patients with ischemic stroke, which closely related to NIHSS score. Human neural stem cells (hNSCs) were used for characterization and subcellular localization of circRNA_102046, and hNSCs OGD/R model was generated. The proliferation of cells was examined by CCK-8 assay. The expression levels of associated molecules were evaluated using RT-qPCR, immunofluorescence staining or western blotting. The binding and co-localization of associated molecules were also evaluated by RIP and FISH assay. Furthermore, MCAO mouse model was established to examine the effects of circRNA_102046 on the progression of ischemic stroke. Expression of circRNA_102046 was detected in the cytoplasma of hNSCs. Then OGD/R cell model was established, where the levels of circRNA_102046 was significantly up-regulated. Furthermore, knockdown of circRNA_102046 was able to enhance the proliferation and differentiation of OGD/R hNSCs. In further downstream molecular studies, the results indicated that circRNA_102046 could participate in the occurrence and development of ischemic stroke through targeting miR-493-5p. In addition, ROCK1 was identified as the putative target of miR-493-5p, and circRNA_102046 regulates the proliferation and differentiation of hNSCs via the miR-493-5p/ROCK1 signaling. More importantly, the infarct volumes of MCAO mice were remarkably reduced after the treatment with sh-circRNA_102046, which also up- and down-regulate the expression of miR-493-5p and ROCK1, respectively. Elucidating this novel pathway provides a theoretical basis for the development of new diagnostic approach and targeted treatment for ischemic stroke."

基金机构："Natural Science Foundation Project of Chongqing, Chongqing Science and Technology Commission"

基金资助正文：None.