Erratum: [Corrigendum] Effects of histone deacetylase inhibitors on ATP­binding cassette transporters in lung cancer A549 and colorectal cancer HCT116 cells.

[This corrects the article DOI: 10.3892/ol.2019.10319.].

CFIm25-regulated lncRNA acv3UTR promotes gastric tumorigenesis via miR-590-5p/YAP1 axis.

Accumulating evidences indicate that 3'UTR of the coding gene can act as crucial regulators in gastric cancer (GC). However, the detailed mechanisms and responsive targets are not well established. Here, we found that acvr1b gene 3'UTR (acv3UTR) was elevated in GC tissue, the expression of which was significantly correlated with advanced pTNM-stage and poor outcome in clinical patients. Forced expression of acv3UTR promoted GC cells growth in vitro and in vivo. Mechanistically, our results suggested that acv3UTR functioned as an oncogenic competing endogenous RNA via sponging miR-590-5p and enhancing YAP1 level. Tumor suppressor miR-590-5p was a molecular module in acv3UTR regulatory axis, the forced expression of which led to impairing of oncogenic potential of acv3UTR. The positive correlation of acv3UTR and YAP1 expression, and the negative correlation of acv3UTR and miR-590-5p expression, were verified in GC patients. Moreover, CFIm25 was identified as a key regulator contributing to acv3UTR aberrant expression in GC binding to UGUA-264 motif. Overall, our finding defines a mechanism for understanding the potential role of acv3UTR transcription in GC tumorigenesis, and indicates a correlation between 3'UTR trans-regulatory effect and GC development.

Effects of histone deacetylase inhibitors on ATP-binding cassette transporters in lung cancer A549 and colorectal cancer HCT116 cells.

Histone deacetylase (HDAC) inhibitors and DNA alkylators are effective components used in combination chemotherapy. In the present study, the effects of HDAC inhibitors on the expression of ATP-binding cassette (ABC) transporters were investigated. It was observed that HDAC inhibitors induced the expression of multidrug-resistant ABC transporters differently in lung cancer A549 cells than in colorectal cancer HCT116 cells. In these two cell lines, the HDAC inhibitors suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) significantly increased ABCB1 expression at the mRNA and protein levels, whereas they had no evident effect on ABCG2 protein expression. SAHA and TSA decreased ABCG2 mRNA expression in A549 cells and had no evident effect on ABCG2 mRNA expression in HCT116 cells. Notably, SAHA and TSA increased the mRNA expression levels of ABCC5, ABCC6, ABCC10, ABCC11 and ABCC12, as well as the protein expression levels of ABCC2, ABCC10 and ABCC12. By contrast, these inhibitors decreased the mRNA expression levels of ABCC1, ABCC2, ABCC3 and ABCC4, as well as the expression of ABCC1 and ABCC3 proteins. Furthermore, SAHA and TSA were found to downregulate HDAC3 and HDAC4, but not HDAC1 and HDAC2. Taken together, the results suggested that HDAC inhibitors work synergistically with DNA alkylators, in part, due to the inhibitory effect of these inhibitors on ABCC1 expression, which translocates these alkylators from inside to outside of cancer cells. These results further suggested the possibility of antagonism when HDAC inhibitors are combined with anthracyclines and other ABCB1 drug ligands in chemotherapy.

Effect of Inhaled Budesonide on Interleukin-4 and Interleukin-6 in Exhaled Breath Condensate of Asthmatic Patients.

BACKGROUND: Studies of interleukin (IL)-4 and IL-6 in the exhaled breath condensate (EBC) of asthmatic patients are limited. This study was to determine the effect of inhaled corticosteroid (ICS) treatment on IL-4 and IL-6 in the EBC of asthmatic patients. METHODS: In a prospective, open-label study, budesonide 200 µg twice daily by dry powder inhaler was administered to 23 adult patients with uncontrolled asthma (mean age 42.7 years) for 12 weeks. Changes in asthma scores, lung function parameters (forced expiratory volume in 1 s [FEV1], peak expiratory flow [PEF], forced expiratory flow at 50% of forced vital capacity [FEF50], forced expiratory flow at 75% of forced vital capacity, maximum mid-expiratory flow rate) and the concentrations of IL-4 and IL-6 in EBC were measured. RESULTS: Both asthma scores and lung function parameters were significantly improved by ICS treatment. The mean IL-4 concentration in the EBC was decreased gradually, from 1.92 ± 0.56 pmol/L before treatment to 1.60 ± 0.36 pmol/L after 8 weeks of treatment (P < 0.05) and 1.54 ± 0.81 pmol/L after 12 weeks of treatment (P < 0.01). However, the IL-6 concentration was not significantly decreased. The change in the IL-4 concentration was correlated with improvements in mean FEV1, PEF and FEF50 values (correlation coefficients -0.468, -0.478, and -0.426, respectively). CONCLUSIONS: The concentration of IL-4 in the EBC of asthmatic patients decreased gradually with ICS treatment. Measurement of IL-4 in EBC could be useful to monitor airway inflammation in asthmatics.

Effects of N-acetylcysteine on Clara cells in rats with cigarette smoke exposure.

BACKGROUND: The number of Clara cells and the Clara cell 16-kDa protein (CC16) levels of the lung decrease in patients with chronic obstructive pulmonary disease (COPD). N-acetylcysteine (NAC) is a powerful antioxidant and can reduce the frequency of acute exacerbations of COPD. But the exact mechanism is unclear. The present study was designed to investigate the effects of NAC on Clara cells in rats with cigarette smoke exposure. METHODS: Eighteen adult male Wistar rats were randomly divided into 3 groups, 12 exposed to cigarette smoke (CS) thrice a day, 10 cigarettes for 30 minutes each time for 1 week, without (CS group) or with (CS + NAC group) oral intake of NAC 80 mg x kg(-1) x d(-1), and another 6 rats exposed to fresh air (control group). Clara cells were observed by an electron microscope. The mRNA expression of CC16 and CC16 protein in lungs were determined by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry respectively. The glutathion (GSH) level in plasma and lung tissue were tested by fluorimetry assay. RESULTS: Compared with the controls, the pathologic score of small airways significantly increased in the CS exposed rats (20.3 +/- 14.7 vs. 53.7 +/- 11.5, P < 0.05). The Clara cell particles in cytoplasm decreased in the CS group (P < 0.05). The percentage of CC16-positive cells in bronchioles in the CS group (27.8 +/- 4.3 and 29.5 +/- 2.4 in terminal bronchioles and respiratory bronchioles, respectively) significantly decreased as compared with the control group (37.1 +/- 3.8 and 43.8 +/- 5.8 in terminal bronchioles and respiratory bronchioles, respectively) (P < 0.05). No significant difference was observed in GSH level ((181 +/- 26) nmol/L in the control group vs. (170 +/- 18) nmol/L in the CS group) between the two groups. After treatment with NAC, the pathologic score of small airways (24.1 +/- 17.5) decreased (P < 0.05). Clara cell particles in cytoplasm of Clara cells increased and GSH level in plasma ((213 +/- 40) nmol/L vs. (170 +/- 18) nmol/L in the CS group) increased too (P < 0.05), while the increase in the proportions of CC16 positive cells in bronchioles (30.1 +/- 6.4 and 34.3 +/- 6.3 in terminal bronchioles and respiratory bronchioles, respectively) did not reach the statistical significance (P > 0.05). No significant difference was found in the expression of CC16 mRNA among the three groups. Correlation analysis indicated that the percentage of CC16-positive cells in bronchioles negatively correlated with the pathologic score of small airways (r = -0.592, P < 0.05), but not with GSH level. CONCLUSIONS: One-week CS exposure decreased the number of Clara cells and the expression of CC16 in bronchioles in rats. NAC might provide protection of the Clara cells from oxidative damage and possibly through the elevation of the synthesis and secretion of CC16. These data indicate that NAC decreases airway inflammation induced by CS via induction of CC16.

[Survey of asthma control and perception in asthmatic outpatients of Beijing urban district].

OBJECTIVE: To evaluate the status of asthma control and asthma perception in asthmatic outpatients of Beijing urban district. METHODS: A questionnaire survey in a face-to-face setting was conducted among 360 asthmatic out-patients, 144 males and 316 females, aged (48 +/- 15), from June 2007 to December 2007 in 3 class 3 first level general hospitals in 3 Beijing urban districts. RESULTS: Among 360 asthmatic patients, 325 (90.3%) enjoyed various kinds of social insurance. During the past year, 12.2% (44/360) of them were in hospital because of asthma exacerbation, 25.6% (92/360) of them had visited emergency department because of asthma exacerbation; the percentage of adults with lost workdays caused by asthma was 29.6% (65/220), and the percentage of children with lost school days was 26.9% (7/26); 87.8% (316/360) of the respondents had undergone a lung-function test, 29.2% (105/360) had ever used peak flow meter; 68.6% (247/360) of these patients had been used inhaled corticosteroids regularly for a long time, and 30.6% (110/360) of them achieved asthma control. CONCLUSIONS: The levels of asthma control and asthma perception among the asthma patients in Beijing have been improved a lot. The asthma perception of the patients influences the control level greatly.