Cerebral ischemia causes damage to the structure and function of the blood‐brain barrier (BBB) and alleviating BBB destruction will be of great significance for the treatment and prognosis of ischemic stroke. Recently, microRNAs have been shown to play a critical role in BBB integrity. However, the potential mechanism by which microRNA‐182 (miR‐182) affects the BBB in ischemic stroke remains unclear. We demonstrated for the first time that cerebral ischemia leads to a significant progressive increase in miR‐182 after pMCAO, and bEnd.3 cells are the primary target cells of miR‐182. In miR‐182 KD transgenic mice, infarct volume, and BBB permeability were attenuated, and tight junction (TJ) proteins increased. Inhibition of miR‐182 with an antagomir reduced OGD‐induced apoptosis of bEnd.3 cells and the loss of ZO‐1 and Occludin. To further explore the mechanism by which miR‐182 regulates BBB integrity, we detected the apoptotic proteins Bcl‐2/Bax and demonstrated that mTOR and FOXO1 were the targets of miR‐182. Inhibition of mTOR/FOXO1 by rapamycin/AS1842856 decreased the ratio of Bcl‐2/Bax and exacerbated TJ protein loss. Taken together, inhibition of miR‐182 protects BBB integrity by reducing endothelial cell apoptosis through the mTOR/FOXO1 pathway. Thus, miR‐182 may be a potential target for the treatment of BBB disruption during cerebral ischemia.

AURKA, a cell cycle‐regulated kinase, is associated with malignant transformation and progression in many cancer types. We analyzed the expression change of AURKA in pan‐cancer and its effect on the prognosis of cancer patients using the TCGA dataset. We revealed that AURKA was extensively elevated and predicted a poor prognosis in most of the detected cancer types, with an exception in colon cancer. AURKA was elevated in colon cancer, but the upregulation of AURKA indicated better outcomes of colon cancer patients. Then we revealed that undermethylation of the AURKA gene and several transcription factors contributed to the upregulation of AURKA in colon cancer. Moreover, we demonstrated that AURKA overexpression promoted the death of colon cancer cells induced by Oxaliplatin, whereas knockdown of AURKA significantly weakened the chemosensitivity of colon cancer cells to Oxaliplatin. Mechanistically, AURKA inhibited DNA damage response by suppressing the expression of various DNA damage repair genes in a TP53‐dependent manner, which can partly explain that ARUKA is associated with a beneficial outcome of colon cancer. This study provided a possibility to use AURKA as a biomarker to predict the chemosensitivity of colon cancer to platinum in the clinic.

Cerebral ischemia-reperfusion injury induces a secondary immune inflammatory reaction that exacerbates brain injury and clinical prognosis. Dendritic cells (DCs) and microglia are both important regulators of neuroinflammation. Studies have confirmed that a large number of cells express the DC surface marker CD11c in the ischemic area, and some of these cells also express microglial markers. However, the specific mechanism of transformation between microglia and DCs and their roles in the process of cerebral ischemia-reperfusion injury are still not clear. In this study, we established a mouse model and flow cytometry was used to detect the expression of mature DC surface molecules in activated microglia. IFN-γ knockout mice were used to determine the regulatory effect of IFN-γ on microglial transformation. We found that CD11c⁺ cells were derived from microglia after ischemia-reperfusion injury, and this group of cells highly expressed MHC-II molecules and other costimulatory molecules, such as CD80 and CD86, which were regulated by IFN-γ and its downstream signaling molecules ERK/c-myc. In summary, our results showed in cerebral ischemia-reperfusion injury, IFN-γ regulates the transformation of microglia to DC-like cells. Microglial-derived DC-like cells possess the ability to present antigens and activate naïve T cells which is regulated by the ERK/c-myc signaling pathway.