In this study, we identified abnormally expressed or spliced RBPs in the microglia of SAH mice by analyzing differentially expressed genes and alternatively spliced genes in the microglia of SAH mice and Sham mice, and established aberrant expression, respectively. It was found that the abnormal expression or abnormal splicing of RBPs such as Mcm7, Mtdh, Srsf3, Hnrnpa2b1 and other RBPs may be variable by regulating downstream protein phosphorylation-related genes, such as Csnk1d and Uckl1, affecting the occurrence and development of microglia- mediated neuroinflammation after SAH.
RBPs are proteins that possess the ability to bind RNA molecules and thereby modulate gene expression and function. In the process of RNA transcription, modification, transport, translation, and degradation metabolism, various specific RBPs bind to them for transcriptional and post-transcriptional regulation. Abnormal expression or functional of RBPs are involved in the development of various diseases, which may be potential therapeutic targets.
The RBPs have an important function in brain injury. After hypoxic-ischemic, RBM 3 promotes neurogenesis through IMP 2-IGF2 signaling pathway in a niche-dependent manner, and inhibited oxygen-glucose deprivation / reoxygenation-induced apoptosis by promoting the formation of stress granules in PC12 cells and rat primary cortical neurons[24]. Rbfox1 was involvement in the expression of CaMKIIα secondary to brain injury induced by cerebral hemorrhage by blocking micro-RNA-124[25].
The RBPs also have important function in neuroinflammation. Prdx-1 has reduced ICH-induced brain damage by targeting the mRNA stability associated with inflammation and apoptosis[26]. The decrease of TIA-1 has aggravated neuroinflammation in Tauopathy[27]. HuR also have promoted Th 17 cell differentiation, which could be targeted to reduce autoimmune neuroinflammation[28]. IMP 2 has driven the stromal-Th 17 cell circuitry in autoimmune neuroinflammation[29].
RBPs affect brain injury and neuroinflammation development by regulating ASEs. and Variable splicing events of RNA are an important source of protein diversity in living organisms. RBM-5 attenuates brain damage by regulating RNA variable splicing[30, 31]. Therefore, RBPs probably participate in regulating RNA splicing and affects neuroinflammation. The absence or abnormal function of RBPs may affect abnormal variable splicing of genes involved in neuroinflammation in the human brain group of Huntington disease, and RBPs are involved in the regulation of RNA variable splicing factor affecting the function of microglia. It is now recognized that ASEs abnormalities of RNA may affect brain development and the development of brain diseases.
This study discovered that the abnormal expression or abnormal splicing of RBPs such as Mcm7, Mtdh, Srsf3, Hnrnpa2b1 may be variable by regulating downstream protein phosphorylation-related genes, such as Csnk1d and Uckl1, affecting the occurrence and development of microglia-mediated neuroinflammation after SAH. However, the present study is limited to the absence of experimental evidence.
The utilization of Mcm7 proliferation index presents a more effective approach for identifying patients at risk of recurrence when compared to the conventional methods currently employed in clinical practice. This suggests that incorporating Mcm7 into diagnostic procedures has the potential to enhance the accuracy of prognosis prediction and treatment decision-making for meningioma patients[32]. Moreover, by directly targeting Mtdh, miR-30b-5p has a direct impact on glioma cell proliferation, highlighting its potential as a promising therapeutic target for treating glioma[33].
The smallest member of the SR protein family is called Ser/Arg-rich splicing factor 3 (SRSF3), is expressed abnormally in cancer cells and is regulated by a variety of variables and intricate mechanisms in eukaryotic cells. We place great importance on highlighting the detrimental effects of the increased expression of the SRSF3 oncogene in cancer development. Additionally, we delve into the mechanisms by which SRSF3 promotes the transformation of cells, as well as the potential implications of lowering SRSF3 expression as a strategy for developing anticancer drugs. The accumulation of research on SRSF3 has provided invaluable knowledge regarding its crucial role in sustaining biological functions, providing fresh targets for possible cancer treatments[34].
It should be emphasized that the presence and quantities of Hnrnpa2b1 have been found to be linked to cancer-associated fibroblasts in various types of cancers, including LUAD,adrenocortical carcinoma, and stomach adenocarcinoma. Furthermore, Hnrnpa2b1 actively participates in pathways related to spliceosome regulation and cell cycle control. And last, for diseases including lung squamous cell carcinoma, LUAD, esophageal carcinoma, breast invasive carcinoma, and liver hepatocellular carcinoma, Hnrnpa2b1 has a very high diagnostic importance.This thorough research highlighted the importance of Hnrnpa2b1 in the development of several cancer types[35].
In all, the findings of RBPs, including Mcm7, Mtdh, Srsf3, Hnrnpa2b1, may provide clues or further verification and revealing of the microglial cell-mediated neuroinflammation function and mechanism of RBPs in SAH, and are of great significance for the identification of new therapeutic targets for brain injury after SAH. Future research could reveal the pathophysiology of SAH-EBI to improve patient outcomes.