Effect of inhibition to Yes-related proteins-mediated Wnt/β-catenin signaling pathway through miR-195-5p on apoptosis of gastric cancer cells

被引:29
作者
Zhao, D-L [1 ]
Wu, Q-L [2 ]
机构
[1] Zhuji Peoples Hosp, Dept Gastrointestinal Surg, Shaoxing, Peoples R China
[2] Zhuji Peoples Hosp, Dept Gen Surg, Shaoxing, Peoples R China
关键词
MiR-195-5p; Yes related protein; Wnt/beta-catenin signaling pathway; Apoptosis; Gastric cancer (GC); MICRORNA; EXPRESSION;
D O I
10.26355/eurrev_201908_18532
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
OBJECTIVE: This clinical study aimed to explore the expression of miR-195-5p and Yes-associated protein (YAP) in gastric cancer (GC) and their relevant apoptosis mechanism. PATIENTS AND METHODS: Thirty GC patients treated in our hospital were enrolled as a patient group and 30 normal people who underwent physical examination during the same period were enrolled as a normal group. The purchased GC cells and human gastric mucous membrane cells were used to transfect miR-195-5p-mimics, miR-NC, si-YAP, and si-RNA into MKN45 and SGC7901 cells. qRT-PCR was used to detect the expression of miR-195-5p and YAP in samples, and WB was used to detect the expression of YAP, Caspase-3, Caspase-9, beta-catenin, c-myc, and cyclin D1. CCK-8, the transwell, and the flow cytometry were used to detect cell proliferation, invasion, and apoptosis. The dual fluorescent enzyme reporter was used to determine the relationship between miR-195-5p and YAP. RESULTS: MiR-195-5p was lowly expressed in the tissues and serum of patients, but YAP was highly expressed, and the area under the miR-195-5p and YAP curves was more than 0.9. MiR-195-5p and YAP were associated with tumor diameter, TNM stage, lymph node metastasis, and differentiation in GC patients. The overexpression of miR-195-5p and the inhibition of YAP expression can inhibit cell proliferation and invasion and promote apoptosis. WB assay showed that the overexpression of miR-195-5p and the inhibition of YAP could inhibit the expression of beta-catenin, c-myc, and cyclin D1 protein and promote the expression of Caspase-3, Caspase-9 protein. The dual fluorescent enzyme reporter revealed that there was a targeting relationship between miR-195-5p and YAP. CONCLUSIONS: The overexpression of miR-195-5p can inhibit YAP-mediated Wnt/beta-catenin signaling pathway and promote cell apoptosis, so it may be a potential therapeutic target for GC.
引用
收藏
页码:6486 / 6496
页数:11
相关论文
共 25 条
[1]   Regulation of Yes-Associated Protein by Laminar Flow [J].
Chitragari, Gautham ;
Shalaby, Sherif Y. ;
Sumpio, Brandon J. ;
Kurita, Jiro ;
Sumpio, Bauer E. .
ANNALS OF VASCULAR SURGERY, 2018, 52 :183-191
[2]   Yes-associated protein regulates endothelial cell contact-mediated expression of angiopoietin-2 [J].
Choi, Hyun-Jung ;
Zhang, Haiying ;
Park, Hongryeol ;
Choi, Kyu-Sung ;
Lee, Heon-Woo ;
Agrawal, Vijayendra ;
Kim, Young-Myeong ;
Kwon, Young-Guen .
NATURE COMMUNICATIONS, 2015, 6
[3]   YAP triggers the Wnt/β-catenin signalling pathway and promotes enterocyte self-renewal, regeneration and tumorigenesis after DSS-induced injury [J].
Deng, Feihong ;
Peng, Liang ;
Li, Zhijun ;
Tan, Gao ;
Liang, Erbo ;
Chen, Shengbo ;
Zhao, Xinmei ;
Zhi, Fachao .
CELL DEATH & DISEASE, 2018, 9
[4]   The Hippo transducers TAZ/YAP and their target CTGF in male breast cancer [J].
Di Benedetto, Anna ;
Mottolese, Marcella ;
Sperati, Francesca ;
Ercolani, Cristiana ;
Di Lauro, Luigi ;
Pizzuti, Laura ;
Vici, Patrizia ;
Terrenato, Irene ;
Sperduti, Isabella ;
Shaaban, Abeer M. ;
Sundara-Rajan, Sreekumar ;
Barba, Maddalena ;
Speirs, Valerie ;
De Maria, Ruggero ;
Maugeri-Sacca, Marcello .
ONCOTARGET, 2016, 7 (28) :43188-43198
[5]   Determination of plasma microRNA for early detection of gastric cancer [J].
Gorur, Aysegul ;
Fidanci, Senay Balci ;
Unal, Nil Dogruer ;
Ayaz, Lokman ;
Akbayir, Serin ;
Yaroglu, Hatice Yildirim ;
Dirlik, Musa ;
Serin, Mehmet Sami ;
Tamer, Lulufer .
MOLECULAR BIOLOGY REPORTS, 2013, 40 (03) :2091-2096
[6]   Differential expression of microRNA species in human gastric cancer versus non-tumorous tissues [J].
Guo, Junming ;
Miao, Ying ;
Xiao, Bingxiu ;
Huan, Rong ;
Jiang, Zhen ;
Meng, Dan ;
Wang, Yanjun .
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 2009, 24 (04) :652-657
[7]   YAP promotes erlotinib resistance in human non-small cell lung cancer cells [J].
Hsu, Ping-Chih ;
You, Bin ;
Yang, Yi-Lin ;
Zhang, Wen-Qian ;
Wang, Yu-Cheng ;
Xu, Zhidong ;
Dai, Yuyuan ;
Liu, Shu ;
Yang, Cheng-Ta ;
Li, Hui ;
Hu, Bin ;
Jablons, David M. ;
You, Liang .
ONCOTARGET, 2016, 7 (32) :51922-51933
[8]   Validation of the 8th Edition of the AJCC TNM Staging System for Gastric Cancer using the National Cancer Database [J].
In, Haejin ;
Solsky, I. ;
Palis, B. ;
Langdon-Embry, M. ;
Ajani, J. ;
Sano, T. .
ANNALS OF SURGICAL ONCOLOGY, 2017, 24 (12) :3683-3691
[9]   Japanese gastric cancer treatment guidelines 2014 (ver. 4) [J].
Japanese Gastric Cancer Association .
GASTRIC CANCER, 2017, 20 (01) :1-19
[10]  
Jemal A, 2011, CA-CANCER J CLIN, V61, P134, DOI [10.3322/caac.20115, 10.3322/caac.21492, 10.3322/caac.20107]