Open AccessMicroRNA-323 suppresses nerve cell toxicity in cerebral infarction via the transforming growth factor-β1/SMAD3 signaling pathway
Author(s) -
Fengli Che,
Hongguang Du,
Jianchao Wei,
Weidong Zhang,
Zhe Cheng,
Yanna Tong
Publication year - 2018
Publication title -
international journal of molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.048
H-Index - 90
eISSN - 1791-244X
pISSN - 1107-3756
DOI - 10.3892/ijmm.2018.4020
Subject(s) - cerebral infarction , downregulation and upregulation , apoptosis , microrna , infarction , biology , nerve growth factor , cell cycle , western blot , cell , medicine , microbiology and biotechnology , ischemia , receptor , biochemistry , myocardial infarction , gene
In the present study, the aim was to investigate the function of microRNA‑323 (miR‑323) in cerebral infarction and its underlying mechanism. A rat model of cerebral infarction was established and hippocampal tissues were analyzed. In addition, to further understand the role of miR‑323, PC12 cells were transfected with miR‑323 mimics or inhibitors and subjected to hypoxia to model cerebral infarction. Reverse transcription‑quantitative polymerase chain reaction was used to measure the expression of miR‑323. A luciferase reporter assay was conducted to analyze miR‑323 target sites the partial sequence of the 3'‑untranslated region of SMAD3 mRNA in vitro. Western blot analysis was also used to analyze transforming growth factor‑β1 (TGF‑β1) and SMAD3 protein expression levels. It was observed that miR‑323 expression was significantly upregulated in rats with cerebral infarction compared with rats in the sham‑control group. In addition, overexpression of miR‑323 induced nerve cell toxicity and reduced nerve cell growth in an in vitro model of cerebral infarction, whereas downregulation of miR‑323 caused the opposite effects on nerve cell toxicity and growth in this model. In addition, overexpression of miR‑323 directly targeted and suppressed SMAD3 expression in the in vitro model of cerebral infarction, while inhibition of miR‑323 induced SMAD3 expression. The use of a SMAD3 inhibitor suppressed the effect of anti‑miR‑323 on nerve cell toxicity in the in vitro model of cerebral infarction. Collectively, these findings suggested that miR‑323 suppresses nerve cell apoptosis in cerebral infarction via the TGF‑β1/SMAD3 signaling pathway.