Background:Increasing evidence has shown that microRNAs (miRNAs) can serve as oncogenes and tumour suppressors to participate in tumour development. However, the roles of miRNAs in chemoresistance of human lung adenocarcinoma (LA) remain largely undefined.Methods:On the basis of miRNA microarray data, miR-224 was identified as the most upregulated miRNA in cisplatin (DDP; cis-diamminedichloroplatinum II)-resistant A549 cells compared with parental A549 cells. The aim of our study was to investigate the roles of miR-224 in the formation of DDP-resistant phenotype of LA cells and its possible molecular mechanisms.Results:Here we showed that miR-224 could promote the in vitro and in vivo DDP resistance of LA cells via regulating G1/S cell cycle transition and apoptosis. p21WAF1/CIP1, a potent cyclin-dependent kinase inhibitor, was identified as the direct and functional target gene of miR-224. Overexpression of p21WAF1/CIP1 could phenocopy the effect of miR-224 downregulation and silencing of p21WAF1/CIP1 could partially reverse the effect of miR-224 downregulation on DDP resistance of DDP-resistant LA cells. In addition, miR-224 could affect the G1/S transition of cell cycle and apoptosis in LA cells through the p21WAF1/CIP1-pRb pathway and the intrinsic mitochondrial death pathway. Furthermore, miR-224 was found to be downregulated in DDP-responding LA tissues, and its expression was inversely correlated with p21WAF1/CIP1. Multivariate analyses indicated that the status of miR-224 might be an independent prognostic factor for predicting the survival of LA patients.Conclusions:Our findings shed novel light on the roles of miR-224/p21WAF1/CIP1 signalling in the DDP resistance of LA cells, and targeting it will be a potential strategic approach for reversing the DDP resistance in human LAs.
Thus, ESWL is a safe and effective method to treat Chinese patients with pancreatic stones. This procedure can significantly improve the success rate of endotherapy.
Objective To evaluate the value of multiple guided technologies based on
radial probe endobronchial ultrasound (R-EBUS) in the application of the diagnosis of
solitary pulmonary peripheral lesions (PPLs).Methods Analysis of diagnostic yield in 4 groups patients with different
combined multiple guided technologies based on R-EBUS, 94 patients with 94 solitary
PPLs from Mar, 2013 to Nov, 2014 in Changhai Hospital.Results The overall diagnostic yield was 75% (70/94), the diagnostic
yield of Group A (R-EBUS) was 62%(16/26), Group B (R-EBUS with guided sheath,
EBUS-GS) was 76% (34/45), Group C (EBUS-GS with fluoroscopy) was 82% (9/11), Group D
(virtual bronchoscopic navigation guided EBUS-GS with fluoroscopy) was 92% (11/12).
The overall histopathological diagnostic yield was 56% (53/94. Better
histopathological diagnostic yield was associated with application of multiple guided
technologies based on EBUS-GS, lesions located in non-lower lobes, lesion's diameter
> 2cm, radial probe within the lesions and lidocaine nebulization combined with
intravenous anesthesia. There were no severe complications in all the 94 cases. A
ultrasonic radial probe was broken when exploring a lesion located in the
apical-posterior segment of left upper lobe.Conclusion Multiple guided technologies based on R-EBUS were safe and
effective in the diagnosis of solitary PPLs. In practice, the diagnosis yield
improved with the application of forcep biopsies combined with bronchial brushing and
washing.
Yes-associated protein (YAP) has been implicated as an oncogene in multiple human cancers. In the present study, human gastric adenocarcinoma tissues of different grades (N=78) were collected and the mRNA and protein expression of YAP and phosphorylated YAP (p-YAP) in gastric adenocarcinomas were evaluated using immunohistochemistry, Real-time PCR and Western blot assays. Then, human gastric cancer SGC-7901 cells were stably transfected with lentivirus-mediated YAP small hairpin RNA (shRNA). The expression levels ofYAP,proliferating cell nuclear antigen (PCNA) and metalloproteinase-2 (MMP-2) were detected and the effects of shRNA-mediated knockdown ofYAP on cell proliferation and metastasis were assessed in gastric cancer cells. As a result, the expression ofYAP was observed in 69.23% gastric adenocarcinoma tissues, elevating with the ascending order of tumor malignancy. Knockdown of YAP could down-regulated the expression of PCNA and MMP-2, and inhibit the proliferation and metastasis of gastric cancer cells. In conclusion, YAP is strongly expressed in gastric adenocarcinomas, and knockdown of YAP may inhibit gastric cancer cell proliferation and metastasis through downregulation of PCNA and MMP-2 expression, suggesting that YAP represents an important therapeutic target in human gastric cancer.
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