Zeitschrift fur die Welt der Turken最新文献

{"title":"MicroRNA-9-5p functions as a tumor suppressor in prostate cancer via targeting UTRN","authors":"Guo, Zhenyu, Huang, Shuchang, Zhou, Yihong, Cheng, Wenjie, Chu, Xi, Zheng, Xiaoqing, Zheng, Hao","doi":"10.17179/excli2019-1512","DOIUrl":"https://doi.org/10.17179/excli2019-1512","url":null,"abstract":"Accumulating evidence indicates that miR-9-5p plays an important role in several diseases, especially tumor progression. In this study, we investigated the clinical significance and biological function of miR-9-5p in prostate cancer (PCa). Using quantitative real time PCR (qRT-PCR) analysis, we found miR-9-5p level was significantly down-regulated in PCa tissues and cell lines. The decreased miR-9-5p expression was associated with tumor size, preoperative PSA, Gleason score and lymph node metastasis. Kaplan-Meier survival analysis showed patients with low level of miR-9-5p had significantly decreased rates of overall survival (OS). Multivariate analyses showed that miR-9-5p was an independent predictor of PCa patients’ prognosis. Through CCK-8 and Transwell assays, miR-9-5p overexpression by miR-9-5p mimics transfection was demonstrated to suppress the proliferation, migration and invasion of PCa cells. Mechanistically, luciferase reporter assay, qRT-PCR and Western blot demonstrated that Utrophin (UTRN) is a direct target of miR-9-5p in PCa cells. The status of UTRN protein in PCa tissues was much higher than that in adjacent tissues by immunohistochemical staining and its mRNA levels were inversely correlated with miR-9-5p in PCa tissues. Importantly, UTRN knockdown by siUTRN imitated the suppressive effects of miR-9-5p on cell proliferation, migration and invasion in PCa. In summary, miR-9-5p might novel prognostic biomarker in and targeting UTRN by miR-9-5p could be potential therapeutic candidates for PCa.","PeriodicalId":33571,"journal":{"name":"Zeitschrift fur die Welt der Turken","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147907854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-intensity ultrasound enhanced the antitumor effects of cisplatin in non-small cell lung cancer cells via inhibiting miR-124/STAT3 signaling","authors":"Peng, Liqing, Luo, Zhijian, Liu, Dan, Feng, Gang, Li, Mingxing","doi":"10.17179/excli2017-910","DOIUrl":"https://doi.org/10.17179/excli2017-910","url":null,"abstract":"Cisplatin (CDDP) is one of the most widely employed first-line chemotherapeutic agent against human non-small cell lung cancer (NSCLC). However, most NSCLC patients are eventually resistant to chemotherapy. Recently, the combined effects of low-intensity ultrasound (US) and several anti-cancer drugs have often been reported, but the underlying mechanism remains largely unknown. This study aimed to test whether low-intensity ultrasound could enhance the anti-tumor effects of cisplatin in NSCLC cells and reveal its underlying molecular mechanism. First, the effects of low-intensity US on cisplatin mediated cell viability, induction of apoptosis and reactive oxygen species (ROS) production were determined by CCK-8 assay, flow cytometry analysis and fluorescent probe (DCFH-DA), respectively. To profile the expression of miRNAs that are involved in the combined effects of cisplatin and low-intensity US, miRNA microarray was applied and the result was verified by quantitative reverse transcription PCR (qRT-PCR). Loss-of-function study was performed to determine the role of miR-124 in the combined effect of cisplatin and low-intensity US exposure. A luciferase reporter assay was performed to validate the interaction between miR-124 and signal transducer and activator of transcription 3 (STAT3) followed by qRT-PCR and Western blot confirmation. Afterward, we further explored whether the effects of miR-124 on the anti-tumor activity of US combined with cisplatin are mediated by STAT3 signaling pathway. Our study showed that low-intensity US enhanced the anti-tumor effects of cisplatin in A549 cells, as evidence by the reduction of cell viability and the induction of apoptosis and ROS levels compared with cisplatin alone treatment. Subsequently, blockade of ROS generation by NAC significantly reversed low-intensity US induced the expression of miR-124, suggesting that cisplatin combined with low-intensity US up-regulated the expression of miR-124 through generation of ROS. Knockdown of miR-124 inhibited the synergistic effects of cisplatin combined with low-intensity US in A549 cells. STAT3, an oncogene, was identified as a direct target of miR-124 and its expression was negatively regulated by miR-124 at mRNA and protein levels. Furthermore, cisplatin combined with low-intensity US decreased the expressions of STAT3 and its downstream genes, phosphorylated STAT3 (p-STAT3), B-cell lymphoma 2 (Bcl-2) and Bcl-xL, whereas knockdown miR-214 reversed the inhibitory effects of cisplatin combined with low-intensity US in A549 cells. In conclusion, our study unraveled low-intensity US enhanced the anti-tumor effects of cisplatin on NSCLC cells and elucidated the participation of miR-124/STAT3 signaling pathway in the synergistic effects of cisplatin combined with low-intensity US. Our findings suggest that low-intensity US can be considered to be a potential strategy for overcoming cisplatin resistance in NSCLC.","PeriodicalId":33571,"journal":{"name":"Zeitschrift fur die Welt der Turken","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147915266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}