Circular RNA circ_0000376 promotes paclitaxel resistance and tumorigenesis of non-small cell lung cancer via positively modulating KPNA4 by sponging miR-1298-5p.

BACKGROUND: Circ_0000376 could promote non-small cell lung cancer (NSCLC) progression; however, the role of circ_0000376 in paclitaxel (PTX) resistance of NSCLC is still unknown. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were applied for measuring circ_0000376, microRNA-1298-5p (miR-1298-5p), and karyopherin subunit alpha 4 (KPNA4) expression. The half inhibitory concentration (IC50) of PTX was assessed by cell counting kit-8 assay. 5-ethynyl-2'-deoxyuridine assay, wound healing assay, transwell assay, and flow cytometry were performed to measure the proliferation, migration, invasion, and apoptosis of cells. The regulatory mechanisms of circ_0000376, miR-1298-5p, and KPNA4 were validated by dual-luciferase reporter assay, RNA immunoprecipitation assay, and rescue experiments. Xenograft assay was used for the functional analysis of circ_0000376 in vivo. RESULTS: Circ_0000376 and KPNA4 expressions were upregulated, while miR-1298-5p expression was downregulated in PTX-resistant tissues and cells. Circ_0000376 depletion promoted PTX sensitivity and apoptosis, while suppressing the proliferation, migration, and invasion of PTX-resistant NSCLC cells. Furthermore, circ_0000376 could modulate KPNA4 expression by sponging miR-1298-5p. Rescue experiments showed that miR-1298-5p inhibition reversed the circ_0000376 depletion-mediated anticancer effects and PTX sensitivity. Moreover, miR-1298-5p inhibited PTX resistance and tumorigenesis of PTX-resistant cells, which were abolished by KPNA4 overexpression. In addition, circ_0000376 knockdown suppressed tumor growth and enhanced PTX sensitivity in vivo. CONCLUSION: Circ_0000376 facilitated PTX resistance and tumorigenesis of NSCLC by miR-1298-5p/KPNA4 axis, suggesting an underlying therapeutic strategy for NSCLC.

Efficacy of continuous positive airway pressure treatment in treating obstructive sleep apnea hypopnea syndrome associated with carotid arteriosclerosis.

Sleep apnea negatively impacts patients' ability to oxygenate the bloodstream during sleep and has far-reaching, deleterious effects. The present study sought to assess the correlation between obstructive sleep apnea hypopnea syndrome (OSAHS), carotid atherosclerosis, and blood pressure variability (BPV), and to evaluate the therapeutic effects of continuous positive airway pressure (CPAP). Patients with OSAHS were classified as mild, moderate, or severe according to their condition and compared with healthy control participants. CPAP treatment was used to treat patients with OSAHS for 6 months. Prior to CPAP treatment, the apnea-hypopnea index (AHI), lowest blood oxygen saturation (LSaO2), carotid intima media thickness (IMT), and plasma levels of endothelin-1 (ET-1), nitric oxide (NO), and tumor necrosis factor-α (TNF-α) were measured in all participants, along with the low frequency components of BPV (BPV LF). The results demonstrated that carotid IMT, AHI, plasma ET-1, and plasma TNF-α were significantly higher in patients with OSAHS than those in the control group (P<0.05); whereas LSaO2 and plasma NO levels were significantly higher in the control group (P<0.05). The degree to which these indices differed was associated with the severity of OSAHS. Furthermore, the carotid IMT of patients with OSAHS was significantly correlated with AHI (P=0.037), plasma ET-1 (P=0.001), plasma NO (P<0.001), BPV LF before retiring (P<0.001). Following CPAP treatment, the observation indices of patients with moderate or severe OSAHS improved significantly (P<0.01). These results support the use of CPAP to improve the significant vascular endothelial dysfunction, increased inflammatory response, and high blood pressure variability correlated with carotid atherosclerosis observed in patients with OSAHS.