Ischemic stroke (IS) is a cerebrovascular disease with serious neurological function impairment, which may activate endoplasmic reticulum (ER) stress. However, the underlying regulatory mechanism of ER stress under IS remains unclear. miR-9-5p is enriched in the brain tissues and plays a role in the pathological process of IS. Therefore, the purpose of this study is to explore the effect of miR-9 on ER stress and underlying mechanism in IS. Here, a middle cerebral artery occlusion (MCAO) rat model was utilized to examine the alteration of brain pathology, and the expressions of miR-9 and ER stress-related proteins. Then SH-SY5Y cells with oxygen-glucose deprivation (OGD) were performed to further evaluate the functional role of miR-9 and preliminary mechanism. The results showed that miR-9 levels were decreased in the ischemic region of rats after MCAO. MCAO significantly increased the brain infract volume, reduced Nissl bodies and cell apoptosis , and increased ER stress-related proteins (ERMP1, GRP78, p-PERK, p-eIF2α and CHOP). Furthermore, overexpression of miR-9 by miR-9 mimics increased cell viability , inhibited LDH activity and cell apoptosis, and inactivated ER stress in OGD-neurons. Luciferase activity results showed that miR-9 negatively regulated ERMP1 expression by directly targeting ERMP1 3′ UTR. Subsequently, we found that ERMP1 overexpression reversed the inhibition of miR-9 on GRP78-PERK−CHOP pathway in OGD neurons. In summary, our results suggest that the attenuation of miR-9 on ischemic injury may be involved in targeting ERMP1-mediated ER stress, which provides an available target for IS treatment.
Anaplastic thyroid carcinoma (ATC) has a poor prognosis due to its resistance to all conventional treatments. The long non‑coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) serves a critical role in cancer chemoresistance; however, whether NEAT1 is associated with chemoresistance of ATC remains unclear. In the present study, reverse transcription‑quantitative PCR assays were performed to detect the expression levels of NEAT1, microRNA (miR)‑9‑5p and sperm‑associated antigen 9 (SPAG9). Western blot analysis was conducted to assess the protein expression levels of p62, microtubule‑associated proteins 1A/1B light chain 3B and SPAG9. Cell proliferation was detected using the Cell Counting kit‑8 assay, and cell apoptosis was determined by flow cytometry. Dual‑luciferase reporter and RNA immunoprecipitation assays were performed to verify the interaction between NEAT1 and miR‑9‑5p, or miR‑9‑5p and SPAG9. Furthermore, an animal model was used to investigate the regulatory effects of NEAT1 on cisplatin (DDP)‑resistance in tumors in vivo. The present results demonstrated that NEAT1 was upregulated in ATC tissues and cell lines, and NEAT1 silencing resulted in decreased DDP‑resistance of ATC cells. In addition, NEAT1 suppressed miR‑9‑5p expression by binding to miR‑9‑5p and SPAG9 was a direct target of miR‑9‑5p. miR‑9‑5p overexpression sensitized ATC cells to DDP. Notably, NEAT1 silencing exerted its inhibitory effect on DDP‑resistance of ATC via the miR‑9‑5p/SPAG9 axis in vitro and in vivo. In conclusion, the present study demonstrated that NEAT1 silencing ameliorated DDP‑resistance of ATC, at least in part by reducing miR‑9‑5p sponging and regulating SPAG5 expression; therefore, NEAT1 may be considered a potential therapeutic target of ATC.
The clinical indications reveal that traumatic brain injury (TBI) accelerates the process of limb bone regeneration. However, the mechanisms underlying this phenomenon remain ambiguous. In this inquiry, the activation of endogenous neural stem cells in the hippocampus post TBI led to the secretion of extracellular vesicles (NSC-EV) that targeted bone marrow mesenchymal stem cells, ultimately promoting bone healing. The enrichment of miR-9-5p in NSC-EV facilitated osteogenesis through the activation of the MAP3K3 pathway. We also present a novel hydrogel formulation for clinical application of NSC-EVs by means of ROS-responsive EV delivery. The hydrogel was cross-linked with EVs to create a water-based gel encapsulation, which was applied to a 3D-printed β-TCP scaffold for controlled long-term release that corresponded to those of physiological bone tissue. Our investigation represents the inaugural usage of EVs derived from neural stem cells in bone tissue engineering. These EVs were found to encourage information exchange between the central nervous system and bone tissue regeneration. Our composite scaffold demonstrated impressive bone regeneration qualities in rats with cranial defects, highlighting its potential for pioneering approaches in bone tissue engineering and innovative medical technologies for clinical applications.
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