Decreased MiR-485-5p Contributes to Inflammatory Pain Through Post-Transcriptional Upregulation of ASIC1 in Rat Dorsal Root Ganglion.

BACKGROUND: Inflammatory pain is the most common type of pain treated clinically. However, the currently available treatments for inflammatory pain have limited effects and can cause severe side effects. The aim of this study is to describe the effect of miRNA-485-5p on osteoarthritis-related inflammatory pain. METHODS: Paw withdrawal threshold (PWT) of rats was measured by von Frey filaments. The expressions of miRNA-485-5p and acid-sensing ion channel 1 (ASIC1) in the dorsal root ganglion (DRG) were measured with real-time quantitative PCR and Western blotting analysis. Fluorescent in situ hybridization and fluorescent immunohistochemistry were employed to detect expression of miRNA-485-5p, acid-sensing ion channelASIC1 and co-location of miRNA-485-5p with ASIC1. RESULTS: The PWT of rats was significantly reduced after complete Freund's adjuvant (CFA) injection. The miRNA-485-5p expression level clearly decreased while the ASIC1 expression level was upregulated in the L4-6 dorsal root ganglion (DRG) of CFA rats. MiRNA-485-5p and ASIC1 were co-expressed in the same DRG cells of CFA rats. Amiloride, an inhibitor of ASIC1, clearly increased the PWT of CFA rats. Further, miRNA-485-5p agomir reversed the upregulation of ASICI1 and alleviated CFA-induced mechanical hypersensitivity of CFA rats. CONCLUSION: These results suggest that reduced expression of miRNA-485-5p contributes to inflammatory pain through upregulating ASIC1 expression, implying a promising strategy for pain therapy.

Deubiquitinase UCHL5 is elevated and associated with a poor clinical outcome in lung adenocarcinoma (LUAD).

Lung cancer is one of the most common malignant tumors in the world, with a high rate of malignancy and mortality. Seeking new biomarkers and potential drug targets is urgent for effective treatment of the disease. Deubiquitinase UCHL5/UCH37, as an important component of the 26S proteasome, plays critical roles in ubiquitinated substrate degradation. Although previous studies have shown that UCHL5 promotes tumorigenesis, its role in lung cancer remains largely unknown. In this study, we evaluated the expression and clinical significance of UCHL5 in non-small cell lung cancer (NSCLC). The results demonstrated that the UCHL5 expression level was significantly upregulated in NSCLC tissues compared with the adjacent noncancerous tissues. The level of UCHL5 was associated with tumor size, lymph node invasion, TNM stage and malignant tumor history in patients with lung adenocarcinoma (LUAD). Importantly, high UCHL5 expression predicted a poor overall survival (OS) and a poor disease-free survival (DFS) in patients with LUAD. Univariate regression analysis showed that tumor size, lymph node invasion, TNM stage and UCHL5 expression were associated with OS and DFS in patients with LUAD. The multivariate analysis indicated that the UCHL5 expression level was an independent prognostic factor for OS (HR=1.171, 95% CI=1.052-1.303) and DFS (HR=1.143, 95% CI=1.031-1.267) in these patients. UCHL5 knockdown in LUAD cells significantly inhibited cell proliferation and reduced the expression of key cell cycle proteins. These findings indicate that UCHL5 may serve as a potential prognostic marker and a new therapeutic target for patients with LUAD.

Correlations of coagulation indexes and inflammatory changes with the prognosis of lung cancer complicated with thromboembolic disease.

PURPOSE: To investigate the correlations of coagulation indexes and inflammatory changes with the prognosis of lung cancer (LC) patients complicated with thromboembolic (TE) disease. METHODS: A total of 84 LC patients complicated with TE disease admitted to hospital from January 2010 to January 2016 were enrolled in this study and their clinical data were retrospectively analyzed. A 2-year post-treatment follow-up was carried out. According to the prognosis, patients were divided into 2 groups as dead group (n=25) and alive group (n=59). The coagulation indexes and inflammatory factor levels before low-molecular weight heparin (LMWH) treatment and on the 1st, 3rd, and 7th day after treatment were compared between the two groups. Their relations with the prognosis of patients were analyzed using Pearson method. RESULTS: No statistically significant difference was found in the prothrombin time (PT), levels of Fibrinogen (FIB), D-Dimer (D-D), Interleukin-6 (IL-6) and Procalcitonin (PCT), and activated partial thromboplastin time (APTT) before treatment between the two groups (p>0.05). The PT and levels of FIB, D-D, IL-6, and PCT on the 1st, 3rd, and 7th day after treatment were significantly increased in the dead group compared to those in the alive group, while the APTT was remarkably shortened. Moreover, the PT was gradually prolonged and FIB, D-D, IL-6 and PCT levels were increased in the dead group , but the APTT was gradually shortened over time (p<0.05). The poor prognosis of LC patients complicated with TE disease was positively correlated with PT, FIB, D-D, IL-6 and PCT, but negatively correlated with APTT (p<0.05). CONCLUSION: The poor prognosis of LC complicated with TE disease has positive correlations with PT, FIB, D-D, IL-6 and PCT, and a negative association with APTT, providing a certain reference as a prognostic value in the diagnosis and treatment.

Exploratory analysis of introducing next-generation sequencing-based method to treatment-naive lung cancer patients.

BACKGROUND: The utilization of cancer-linked genetic alterations for categorizing patients against optimal treatment is becoming increasingly popular, especially in non-small cell lung cancer (NSCLC). However, disadvantages of the conventional techniques, such as the low throughput and limited detectable alteration types, lead to the demand of large-scale parallel sequencing for different forms of genetic variants. METHODS: We evaluated the potential of performing next-generation sequencing (NGS)-based methods in a cohort of 61 treatment-naive NSCLC patients to profile their driver mutations, using a panel consisting of 8 well-established driver genes of lung cancer. RESULTS: Our data revealed that 80% of patients harbored driver mutations. Moreover, our data revealed a few rare mutations, such as BRAF K601E and EGFR exon 20 insertion, which cannot be detected using commercially available single gene testing kits of conventional methods. We detected one patient with dual driver mutations. Next, correlations between driver mutations and clinical characteristics were interrogated in this cohort. Our results revealed that EGFR alterations were positively correlated with early stage, adenocarcinoma, alveolar and papillary component, TTF1 expression, and negatively correlated with P40 and Ki67 expression. ERBB2 alterations were associated with younger age and micro-invasive feature of tumor. Rearrangements of ALK indicated tumor relapse. CONCLUSIONS: Our study highlights the potential of NGS-based methods in treatment-naive patients, thus paving its way for routine clinical use. Investigation of clinical correlation of driver mutations might be helpful for clinicians in cancer diagnosis and has implications for seeking patients with specific gene alteration in clinical studies.