No abstract

Extracellular vesicles (EVs) have the potency to function as modulators in the process of myocardial ischemia/reperfusion (I/R) injury. This investigation was performed to decipher the mechanism of human umbilical vascular endothelial cells (HUVECs)-derived EVs in myocardial I/R injury with the involvement of microRNA-129 (miR-129). HUVECs-secreted EVs were collected and identified.An I/R mouse model was developed, and cardiomyocytes were used for vitro oxygen-glucose deprivation/reperfusion model establishment. Differentially expressed miRNAs in myocardial tissues after EV treatment were assessed using microarray analysis. The target relationship between miR-129 and tolllike receptor 4 (TLR4) was identified using a dual-luciferase assay. Gain-and loss-function studies regarding miR-129 were implemented to figure out its roles in myocardial I/R injury. Meanwhile, the activation of the nuclear factorkappa-binding (NF-κB) p65 signaling and NOD-like receptor 3 (NLRP3) inflammasome was evaluated. EVs diminished the apoptosis of cardiomyocytes and the secretion of inflammatory factors, and all these trends were reversed by miR-129 reduction. miR-129 bound to the 3′-untranslated region of TLR4 directly. The NF-κB p65 signaling and NLRP3 inflammasome were abnormally activated after I/R injury, whose impairment after EVs was partially restored by miR-129 downregulation. This study illustrated that EVs could carry miR-129 to mitigate myocardial I/R injury via downregulating TLR4 and disrupting the NF-κB signaling and NLRP3 inflammasome.

Gastric cancer (GC) is the fifth most commonly diagnosed malignant disease and the third leading cause of cancer‑related deaths worldwide. Recently, numerous microRNAs (miRNAs) have been determined to contribute to GC initiation and progression, suggesting that miRNAs may be developed as effective diagnostic and prognostic molecular biomarkers and can be investigated as therapeutic targets for patients with this disease. Therefore, further investigation of the miRNAs involved in GC development represents an opportunity to improve the prognosis of GC patients. miRNA‑454 (miR‑454) is abnormally expressed in multiple types of human cancer. However, the expression pattern, biological roles and underlying mechanism of miR‑454 in GC remain unclear and require further investigation. In the present study, we assessed miR‑454 expression in GC tissues and cell lines. We also explored the effects of miR‑454 on the biological behaviours of tumour cells and the underlying molecular mechanisms of miR‑454. The results revealed that miR‑454 was significantly downregulated in GC tissues and cell lines. Low miR‑454 expression was positively associated with lymph node metastasis, invasive depth and TNM stage. Additionally, upregulation of miR‑454 inhibited cell proliferation and invasion and induced the apoptosis of the GC cells. Subsequently, mitogen‑activated protein kinase 1 (MAPK1) was identified as a direct target of miR‑454. MAPK1 was upregulated in GC tissues and was found to be negatively correlated with the miR‑454 expression level. Downregulation of MAPK1 also suppressed GC cell proliferation and invasion and increased apoptosis, thereby resembling the suppressive effects of miR‑454 overexpression in GC. Moreover, upregulation of MAPK1 reversed the tumour‑suppressive effects of miR‑454 in GC. Collectively, our data demonstrated that miR‑454 may play tumour‑suppressing roles in GC through the regulation of MAPK1, suggesting that miR‑454 may be a novel biomarker and therapeutic target for patients with this disease.

Following the publication of this paper, the authors have been unable to obtain consistent results after having repeated some of the flow cytometric assay experiments, undermining their confidence in the reported conclusions concerning the regulatory action of miR-454 on gastric cancer cell apoptosis. Consequently, owing to a lack of confidence in the presented data, the authors have requested that this paper be retracted from the journal.All authors agree with the retraction of this article, and apologize to the Editor and readership for the inconvenience caused.