Clinical Values and Underlying Mechanism Analysis of Serum miR-455-5p in Carotid Artery Stenosis.

Purpose: Carotid artery stenosis (CAS) is a leading cause of cerebral infarction, its early diagnosis and intervention are necessary. In light of the important role of microRNAs (miRNAs) in cerebrovascular disease, this study aimed to investigate the expression pattern and clinical significance of serum miR-455-5p in the onset and development of CAS, as well as its underlying mechanism. Patients and Methods: Seventy patients with asymptomatic CAS were recruited, and the development of cerebral ischemia events (CIEs) was recorded during the five-years follow-up. qRT-PCR was performed for the serum miR-455-5p detection. ROC curve was applied for the diagnostic ability evaluation. By constructing multivariable logistic or cox regression model, odds ratio (OR) or hazard ratio (HR) were calculated to assess the impact of each risk factor on independent variables. Human aortic endothelial cells (HAECs) were treated with ox-LDL to induce endothelial cell damage. The role of miR-455-5p in the cell viability, apoptosis, oxidative stress and inflammatory response was detected. Results: Serum miR-455-5p showed low expression in cases with CAS, and had an independent influence on the degree of CAS. The diagnostic ability of serum miR-455-5p to diagnose CAS was determined via ROC curve, with the AUC of 0.927. During follow-up, patients with low miR-455-5p expression showed high incidence of CIEs. In multivariable cox regression model, degree of CAS and miR-455-5p were significant risk factors for the development of CIEs in the CAS patients. In vitro, miR-455-5p was at a low expression in HAECs cell models and can prevent cells from ox-LDL induced cell apoptosis, oxidative stress and inflammatory response. SOCS3 was a target gene of miR-455-5p and upregulated in ox-LDL treated cells. Conclusion: Down-regulated expression of serum miR-455-5p is hopeful to be used as a biomarker for the early diagnosis of CAS. MiR-455-5p is an independent risk factor for the degree of CAS, and has a certain predictive value for the development of CIEs. That might be associated with the protective role of miR-455-5p against ox-LDL-induced endothelial cell injury via targeting SOCS3.

LINC01635, a long non-coding RNA with a cancer/testis expression pattern, promotes lung cancer progression by sponging miR-455-5p.

Long non-coding RNAs (lncRNAs) have been reported to play vital roles in human lung cancer. In recent years, cancer/testis (CT) lncRNAs have been characterized as a novel class of lncRNA. However, this class of lncRNA remains to be thoroughly investigated. The present study identified long intergenic non-protein coding RNA 1635 (LINC01635), which was highly expressed in testis and in a broad range of human cancer types. Next, it was confirmed that LINC01635 was upregulated significantly in samples from patients with lung cancer and in non-small cell lung carcinoma (NSCLC) cell lines. Silencing LINC01635 suppressed the proliferation and metastasis of NSCLC cells in vitro and in vivo. Furthermore, it was found that LINC01635 could bind to microRNA (miRNA or miR)-455-5p and regulate the expression of a series of miR-455-5p-targeting tumor-related genes. Knockdown of miR-455-5p partially rescued the progression of lung cancer cells that was suppressed by LINC01635 silencing. Together, the current results demonstrated that LINC01635 may play important roles in NSCLC progression by targeting miR-455-5p, and that it could be a biomarker and therapeutic target for lung cancer.

microRNA-455-5p alleviates neuroinflammation in cerebral ischemia/reperfusion injury.

Neuroinflammation is a major pathophysiological factor that results in the development of brain injury after cerebral ischemia/reperfusion. Downregulation of microRNA (miR)-455-5p after ischemic stroke has been considered a potential biomarker and therapeutic target for neuronal injury after ischemia. However, the role of miR-455-5p in the post-ischemia/reperfusion inflammatory response and the underlying mechanism have not been evaluated. In this study, mouse models of cerebral ischemia/reperfusion injury were established by transient occlusion of the middle cerebral artery for 1 hour followed by reperfusion. Agomir-455-5p, antagomir-455-5p, and their negative controls were injected intracerebroventricularly 2 hours before or 0 and 1 hour after middle cerebral artery occlusion (MCAO). The results showed that cerebral ischemia/reperfusion decreased miR-455-5p expression in the brain tissue and the peripheral blood. Agomir-455-5p pretreatment increased miR-455-5p expression in the brain tissue, reduced the cerebral infarct volume, and improved neurological function. Furthermore, primary cultured microglia were exposed to oxygen-glucose deprivation for 3 hours followed by 21 hours of reoxygenation to mimic cerebral ischemia/reperfusion. miR-455-5p reduced C-C chemokine receptor type 5 mRNA and protein levels, inhibited microglia activation, and reduced the production of the inflammatory factors tumor necrosis factor-α and interleukin-1ß. These results suggest that miR-455-5p is a potential biomarker and therapeutic target for the treatment of cerebral ischemia/reperfusion injury and that it alleviates cerebral ischemia/reperfusion injury by inhibiting C-C chemokine receptor type 5 expression and reducing the neuroinflammatory response.

Long non-coding RNA GAS5 retards neural functional recovery in cerebral ischemic stroke through modulation of the microRNA-455-5p/PTEN axis.

OBJECTIVE: Cerebral ischemic stroke (IS) threatens the daily life of individuals, with high mortality. Emerging studies have deciphered the independent roles of the long non-coding RNA growth-arrest-specific transcript 5 (GAS5), microRNA (miR)-455-5p and phosphatase and tensin homolog (PTEN) in IS, but the understanding of their integrated function is in its infancy. Therefore, this study focusing on the GAS5/miR-455-5p/PTEN axis was initiated. METHODS: Middle cerebral artery occlusion (MCAO) models were established by the suture method. GAS5, miR-455-5p and PTEN expression was detected in rat brain tissues after MCAO. Rats were injected with sh-GAS5 or miR-455-5p agomir before MCAO modeling. A neurobehavioral evaluation was conducted, and oxidative stress injury, apoptosis and mitochondrial function were detected in brain tissues of IS rats. The relationships between GAS5 and miR-455-5p, and between miR-455-5p and PTEN were verified. PC12 cells were transfected with sh-GAS5 or miR-455-5p mimic under oxygen and glucose deprivation/reoxygenation (OGD/R) conditions to evaluate cell viability and apoptosis. RESULTS: GAS5 and PTEN expression levels were elevated and miR-455-5p expression was reduced in brain tissues of MCAO rats and OGD/R-induced PC12 cells. GAS5 downregulation or miR-455-5p upregulation improved neurobehavior, attenuated apoptosis and oxidative injury, and relieved mitochondrial damage in brain tissues of IS rats. Silencing GAS5 or restoring miR-455-5p minimized OGD/R-induced cell damage. MiR-455-5p downregulation antagonized the effects of GAS5 inhibition on IS. CONCLUSION: This work elucidates that GAS5 downregulation upregulates miR-455-5p to repress PTEN expression, in turn attenuating IS, which may broaden the horizon of IS treatment.

Expression profile and biological function of miR-455-5p in colorectal carcinoma.

Underexpression of microRNA-455-5p (miR-455-5p) in medullary thyroid carcinoma, melanoma, gastric cancer and additional cancer types has been reported, which may be associated with carcinoma development. The present study aimed to evaluate the expression profile and biological role of miR-455-5p in colorectal carcinoma. Carcinoma tissues and adjacent tissue specimens from 40 patients with colorectal cancer were randomly collected. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis was conducted to detect the expression levels of miR-455-5p in colorectal carcinoma and adjacent normal tissues. The biological effects of miR-455-5p on selected colorectal cancer cells were assessed using bromodeoxyuridine assays, wound healing migration assays and flow cytometry. Bioinformatics analysis was implemented to predict the potential target genes of miR-455-5p in colorectal cancer. The expression levels of target genes were further validated by RT-qPCR and western blot analysis of the mRNA and protein levels. The results of the experiments demonstrated that miR-455-5p expression was downregulated in colorectal cancer tissues compared with adjacent normal tissues. In colorectal cancer cells (SW-480, HT-29 and HCT-116), miR-455-5p was observed to inhibit cell proliferation and migration while promoting cell apoptosis. Bioinformatics analysis predicted that the oncogene phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) was one of the top ranked target genes of miR-455-5p in colorectal cancer cells. This association was validated by RT-qPCR and western blotting. In vivo studies revealed that the expression level of miR-455-5p was significantly downregulated in human colorectal cancer. Further in vitro studies suggested that miR-455-5p may prevent the development of colorectal cancer by downregulating the oncogene PIK3R1. It was concluded that miR-455-5p may target and downregulate PIK3R1 in colorectal cancer.

Inhibitory effect of microRNA-455-5p on biological functions of esophageal squamous cell carcinoma Eca109 cells via Rab31.

The aim of the present study was to examine microRNA (miRNA or miR)-455-5p expression in esophageal squamous cell carcinoma (ESCC) at the tissue and cellular levels in order to elucidate its biological roles. A total of 60 patients with ESCC were enrolled in the present study and reverse transcription-quantitative polymerase chain reaction was used to measure the expression of miR-455-5p. ESCC Eca109 cells were transfected with miR-NC, miR-455-5p mimics or inhibitor and a Cell Counting Kit-8 assay was used to assess proliferation. To investigate the migration and invasion abilities of Eca109 cells, Transwell and Matrigel assays were performed. Western blotting was employed to measure Rab31 protein expression, while a rescue assay was utilized to study the biological roles of miR-455-5p and Rab31 in Eca109 cells. To determine whether Rab31 is a direct target of miR-455-5p, a dual luciferase reporter assay was performed. The results revealed that miR-455-5p expression was decreased in ESCC tissues and was negatively correlated with metastasis and pathogenesis. In vitro overexpression of miR-455-5p inhibited the proliferation, migration and invasion of ESCC Eca109 cells. Furthermore, miR-455-5p regulated the expression of Rab31 protein in Eca109 cells. Rab31 overexpression promoted the proliferation, migration and invasion of Eca109 cells. Luciferase reporter assay results revealed that miR-455-5p is able to bind with the 3'-untranslated region of Rab31 mRNA to regulate its expression. In summary, the results of the present study suggest that miR-455-5p expression is decreased in ESCC tissues and is miR-455-5p is negatively correlated with lymphatic metastasis and differentiation. As a tumor-suppressor gene, miR-455-5p inhibits the proliferation, migration and invasion of ESCC Eca109 cells by suppressing the expression of Rab31.