miR-1287-5p upregulation inhibits the EMT and pro-inflammatory cytokines in LPS-induced human nasal epithelial cells (HNECs).

BACKGROUND: Chronic rhinosinusitis is an intractable symptom that influences daily lives of patients. miR-1287-5p was discovered to play a suppressive role in cervical cancer and HBV-related infection. PURPOSE: This study investigated the potential role of miR-1287-5p in the in-vitro model of chronic rhinosinusitis. METHODS: GSE169376 dataset was analyzed and differential miRNAs in nasal mucosa tissues in the chronic rhinosinusitis group were screened out. LPS was used to treat HNECs for 12h, 24h and 48h. Cells underwent LPS treatment after SNAI1 downregulation, miR-1287-5p upregulation or pretreatment of the HMGB1 inhibitor, Glycyrrhizin. RT-PCR was used to measure the RNA expression of miR-1287-5p, SNAI1 and HMGB1. ELISA was used for the detection of IL-6, IL-8, TNF-α changes. Targetscan and starBase were used to predict the targets (SNAI1 and HMGB1) of miR-1287-5p. Dual-luciferase reporter assays were applied to validate this. Western blot was used to analyze the protein changes of Snai1, Vimentin, E-cadherin and HMGB1. RESULTS: miR-1287-5p was downregulated in the chronic rhinosinusitis group and decreased after LPS treatment in HNECs. The upregulation of miR-1287-5p inhibited IL-6, IL-8, TNF-α and EMT. miR-1287-5p targeted and inhibited SNAI1 and HMGB1. SNAI1 downregulation led to inhibition in EMT while loss of HMGB1 contributed to the decrease in pro-inflammatory cytokines. Knockdown of SNAI1 decreased HMGB1, resulting in the reduction of pro-inflammatory cytokines while HMGB1 inhibitor reduced SNAI1 and thus suppressed the EMT process. CONCLUSION: miR-1287-5p downregulation was associated with chronic rhinosinusitis and its upregulation inhibited the EMT and inflammation in LPS-induced HNECs through Snai1/HMGB1 pathway.

miR-4270 Modulates the Irradiation-Sensitivity of Nasopharyngeal Carcinoma Cells through Modulation of p53 in Vivo.

The lowered sensitivity to irradiation considerably impacted on the prognosis of nasopharyngeal carcinoma treatments. This study aimed to explore the functions of miR-4270 in nasopharyngeal carcinoma. Bioinformatic analysis was performed online accessing GSE139164 dataset to screen the top 30 differential microRNAs in nasopharyngeal carcinoma patients with radio-sensitivity. Cancer cell lines, 6-10B and 5-8F, were cultured and measured for expression of miR-4270 and TP53 (the gene of the tumor suppressor protein p53) with the normal nasopharyngeal epithelial cells as a control. The miR-4270 expression was regulated in cells via the introduction of miR-4270 inhibitor or mimic in different concentrations (25, 50, 100 nmol/L). Targetscan predicted the target of miR-4270 and the bindings while luciferase was used to confirm this. CCK8 methods were used to evaluate the irradiation sensitivity of the cells after exposure to increasing X-Ray irradiation. RT-PCR detected the RNA expression and Western blot examined the protein expression of p53. Flow cytometry detected the cell apoptosis rates respectively. miR-4270 is among the top differential microRNAs between the radio-sensitive and -resistant patients. In vivo, miR-4270 expression was lower in cancer cell lines. The inhibition of miR-4270 raised the cell sensitivity to irradiation. miR-4270 negatively mediated TP53 and targeted TP53. Additionally, p53 increased cell sensitivity to irradiation and modulated by miR-4270 in nasopharyngeal carcinoma cells. In conclusion, this study first reports that miR-4270 is lower in the radio-sensitive patients and modulated the irradiation-sensitivity of nasopharyngeal carcinoma cells through modulation of p53 in vivo.

Serum paraoxonase, arylesterase activity, and oxidative status in patients with nasal polyp.

The aim of this study was to investigate serum paraoxonase (PON) and arylesterase (ARE) activities, the total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) in the patient with nasal polyp (NP) and control group to confirm the link between oxidative stress and NP. In this prospective study, 32 patients with NP (22 males and 10 females) and 29 healthy controls (19 males and 10 females) were enrolled. Preoperative serum levels of PON, ARE, TAS, and TOS were determined, and OSI was calculated. Serum PON activity, ARE activity, and TAS tend to be decreased in patients with NP compared to healthy controls (P < 0.0001). TOS and OSI levels were significantly higher in the NP patients than in the healthy controls (P < 0.01). Furthermore, there was established positive correlation between serum PON activity and serum ARE activity in patients with NP (r = 0.454; P = 0.009). Our results support the belief that altered PON and ARE activity may be involved in the pathogenesis of NP. Increased TOS and OSI, and decreased TAS indicated that NP is the pathologic consequence of oxidative stress.

Prognostic value of interleukin-6 and interleukin-8 in laryngeal squamous cell cancer.

The aim of this study was to evaluate serum levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) as prognostic variables in patients with laryngeal squamous cell cancer. A total of 92 patients with primary diagnosis of laryngeal squamous cell cancer (LSCC), treated between 2003 and 2005, were included in this evaluation. Preoperative serum levels of IL-6 and IL-8 were measured by enzyme-linked immunosorbent assay methods. Results were compared according to clinical and pathological date criteria. Serum IL-6 and IL-8 levels were significantly higher in patients with LSCC compared to healthy controls (P < 0.0001). Serum IL-6 level was associated with lymph node metastasis (P < 0.001), T classification (P < 0.001) and clinical stage (P = 0.001). Multivariate analysis indicated that serum IL-6 was an independent predictor of LSCC-specific progression-free survival (P = 0.049) and overall survival (P = 0.040). Higher serum IL-6 level (IL-6 > 9.7 pg/ml) was associated with a shortened overall survival and progression-free survival (P < 0.05). Our data indicate that serum IL-6 is associated with the development and progression of LSCC. Serum IL-6 may serve as an independent prognostic marker for LSCC patients.