Jing‐Min Lu

Atherosclerosis is a kind of chronic inflammation disease with lipid accumulation in in blood vessel linings. Increasing evidence has reported that microRNAs can exert crucial roles in atherosclerosis. In previous study, miR‐181a has been implicated to be abnormally expressed in atherosclerosis mice, however its detailed function in atherosclerosis remains uninvestigated. Hence, in our current study, we focused on the biological role of miR‐181a in atherosclerosis progression. Ox‐LDL has been commonly identified as an important atherosclerosis regulator. We observed that ox‐LDL induced THP‐1 cell apoptosis dose‐dependently and time‐ dependently. Meanwhile, 25 µg/ml ox‐LDL can promote foam cell formation and increased miR‐181a expression significantly. CD36 has been involved in atherosclerosis progression and it was found that overexpression of miR‐181a inhibited its protein levels. Moreover, miR‐181a mimics repressed foam cell formation, TC and TG levels induced by ox‐LDL dramatically. In addition, miR‐181a mimics were able to reverse THP‐1 cell apoptosis, increased IL‐6, IL‐1β, and TNF‐α protein expression triggered by 25 µg/ml ox‐LDL. TLR4 has been linked to various inflammation‐associated diseases. In our present study, TLR4 was indicated as miR‐181a target and the binding correlation between them was validated by dual‐luciferase reporter assay. In conclusion, these results improves the understanding of atherosclerosis modulated by miR‐181a/TLR4 and can contribute to development of new approaches for atherosclerosis.

Neuropathic pain is a kind of pain caused by primary or secondary impairment or dysfunction of peripheral or central nervous system. Patients with neuropathic pain were often with poor clinical outcome. We screened the differentially expressed genes between sciatic nerve injury and dorsal root ganglion gene in the sham operation model. Microarray and the spared nerve injury module were used to explore the molecular mechanism of neuropathic pain by injuries and the differentially expressed genes (DEGs) were identified out. Besides, the bioinformatics methods were used to figure out the signaling pathways and expression regulation pattern these DEGs were enriched in, which may provide a basis for the molecular research and medicine target of therapy. Besides, protein‐protein interaction network analysis was performed on these selected intersection genes. A total of 40 DEGs were screened out and only pctp gene was down‐regulated, the left 39 genes were all up‐regulated. Then, GO and KEGG enrichment analysis were performed on these intersection genes by DAVID software. Furthermore, protein‐protein interaction network analysis was used to analyze the critical genes of neuropathic pain. Finally, four genes, that is, Jun, Gal, Cd74, and C1qb were identified to have strong interactions with other genes, which may function as the prognostic and predictive genes of neuropathic pain caused by peripheral injuries. Our results suggested that four differentially expressed genes, Jun, Gal, Cd74, and C1qb, had the potential to serve as prognostic or predictive markers for neuropathic pain, suggesting a potential application in the improvement of prognostic tools and treatments.

LncRNAs are reported to participate in neuropathic pain development. LncRNA X‐inactive specific transcript (XIST) is involved in the progression of various cancers. However, the role of XIST in neuropathic pain remains unclear. In our present study, we established a chronic constriction injury (CCI) rat model and XIST was found to be greatly upregulated both in the spinal cord tissues and in the isolated microglias of CCI rats. Inhibition of XIST inhibited neuropathic pain behaviors including mechanical and thermal hyperalgesia. Moreover, decrease of XIST repressed neuroinflammation through inhibiting COX‐2, tumor necrosis factor (TNF)‐α and IL‐6 and in CCI rats. Previously, miR‐150 has been reported to restrain neuropathic pain by targeting TLR5. Currently, miR‐150 was predicted to be a microRNA target of XIST, which indicated a negative correlation between miR‐150 and XIST. miR‐150 was remarkably decreased in CCI rats and overexpression of miR‐150 can significantly suppress neuroinflammation‐related cytokines. Furthermore, ZEB1 was exhibited to be a direct target of miR‐150 and we found it was overexpressed in CCI rats. Silencing ZEB1 was able to inhibit neuropathic pain in vivo and downreguation of XIST decreased ZEB1, which can be reversed by miR‐150 inhibitors. Taken these together, we indicated that XIST can induce neuropathic pain development in CCI rats via upregulating ZEB1 by acting as a sponge of miR‐150. It was revealed that XIST/miR‐150/ZEB1 axis can be provided as a therapeutic target in neuropathic pain.

MicroRNAs (miRNAs) exhibit various roles in multiple biological processes and abnormal expression of miR‐182‐5p has been involved in many diseases. However, the role miR‐182‐5p in Atherosclerosis (AS) remains poorly understood. In our current investigation, an AS model was established by using oxidized low‐density lipoprotein (ox‐LDL) in RAW264.7 cells. miR‐182‐5p was markedly decreased in AS model dose‐dependently and time‐dependently. Additionally, CD36, oil‐red staining levels, TC, and TG were inhibited by miR‐182‐5p mimics, meanwhile ROS levels, MDA, and cell apoptosis were also restrained with an enhancement of SOD activity. Consistently, opposite results were exhibited when miR‐182‐5p inhibitors were transfected into RAW264.7 cells. It is well known that toll‐like receptor 4 (TLR4) is responsible for many inflammation diseases. By using bioinformatics analysis, TLR4 was indicated as a potential target of miR‐182‐5p. We observed TLR4 was activated in AS models and miR‐182‐5p could repress AS progression by targeting TLR4 in vitro. In conclusion, we uncovered that miR‐182‐5p played significant roles in AS through inhibiting oxidative stress and apoptosis via inactivating TLR4 expression.

E2F3a, as a member of the E2F family, is essential for cell division associated with the progression of many cancers. However, the biological effect of E2F3a on glioma is not understood as well. To investigate the functional mechanism of E2F3a in glioma, we examined the expression of E2F3a in glioma tissue and cell lines. We found that E2F3a was upregulated in glioma tissue compared with adjacent tissue, and this was associated with a poor survival rate. E2F3a was highly expressed in glioma cell lines compared with normal HEB cell lines. Knockdown of E2F3a significantly inhibited cell proliferation, promoted G₀/G₁ phase arrest, elevated apoptosis rates, and suppressed cell migration and invasion. However, overexpression of E2F3a markedly promoted cell proliferation, migration, and invasion and inhibited apoptosis. Moreover, in vivo studies showed that knockdown of E2F3a expression dramatically inhibited U373 tumor growth in a nude mouse model. Results of real-time PCR and Western blot showed that the depletion of E2F3a upregulated the expression levels of cell apoptosis-related proteins and downregulated migration-related proteins. Conversely, E2F3a overexpression downregulated the expression levels of cell apoptosis-related proteins and upregulated migration-related proteins. In conclusion, our results highlight the importance of E2F3a in glioma and provide new insights into the diagnostics and therapeutics of gliomas.

MicroRNAs (miRNAs) are reported as vital participators in the pathophysiological course of neuropathic pain. However, the underlying mechanisms of the functional roles of miRNAs in neuropathic pain are largely unknown. This study was designed to explore the potential role of miR‐150 in regulating the process of neuropathic pain in a rat model established by chronic sciatic nerve injury (CCI). Overexpression of miR‐150 greatly alleviated neuropathic pain development and reduced inflammatory cytokine expression, including COX‐2, interleukin IL‐6, and tumor necrosis factor (TNF)‐α in CCI rats. By bioinformatic analysis, 3′‐untranslated region (UTR) of Toll‐like receptor (TLR5) was predicted to be a target of miR‐150. TLR5 commonly serves as an important regulator of inflammation. Overexpression of miR‐150 significantly suppressed the expression of TLR5 in vitro and in vivo. Furthermore, upregulation of TLR5 decreased the miR‐150 expression and downregulation of TLR5 increased miR‐150, respectively. Overexpression of TLR5 significantly reversed the miR‐150‐induced suppressive effects on neuropathic pain. In conclusion, our current study indicates that miR‐150 may inhibit neuropathic pain development of CCI rats through inhibiting TLR5‐mediated neuroinflammation. Our findings suggest that miR‐150 may provide a novel therapeutic target for neuropathic pain treatment.

Prognostic value of DNA repair genes based on stratification of glioblastomas Prognostic value of DNA repair genes based on stratification of glioblastomas

Glioblastoma multiforme is the most common primary brain tumor and is highly lethal. This study aims to figure out signatures for predicting the survival time of patients with glioblastoma multiforme. Clinical information, messenger RNA expression, microRNA expression, and single-nucleotide polymorphism array data of patients with glioblastoma multiforme were retrieved from The Cancer Genome Atlas. Patients were separated into two groups by using 1 year as a cutoff, and a logistic regression model was used to figure out any variables that can predict whether the patient was able to live longer than 1 year. Furthermore, Cox’s model was used to find out features that were correlated with the survival time. Finally, a Cox model integrated the significant clinical variables, messenger RNA expression, microRNA expression, and single-nucleotide polymorphism was built. Although the classification method failed, signatures of clinical features, messenger RNA expression levels, and microRNA expression levels were figured out by using Cox’s model. However, no single-nucleotide polymorphisms related to prognosis were found. The selected clinical features were age at initial diagnosis, Karnofsky score, and race, all of which had been suggested to correlate with survival time. Both of the two significant microRNAs, microRNA-221 and microRNA-222, were targeted to p27^Kip1 protein, which implied the important role of p27^Kip1 on the prognosis of glioblastoma multiforme patients. Our results suggested that survival modeling was more suitable than classification to figure out prognostic biomarkers for patients with glioblastoma multiforme. An integrated model containing clinical features, messenger RNA levels, and microRNA expression levels was built, which has the potential to be used in clinics and thus to improve the survival status of glioblastoma multiforme patients.