RETRACTED: MicroRNA-148a suppresses epithelial-mesenchymal transition and invasion of pancreatic cancer cells by targeting Wnt10b and inhibiting the Wnt/β-catenin signaling pathway (Retracted article. See vol. 49, 2023)

被引:53
作者
Peng, Long [1 ]
Liu, Zhanying [1 ]
Xiao, Jian [1 ]
Tu, Yi [2 ]
Wan, Zhen [1 ]
Xiong, Haiwei [1 ]
Li, Yong [1 ]
Xiao, Weidong [1 ]
机构
[1] Nanchang Univ, Affiliated Hosp 1, Dept Gen Surg, Nanchang 330006, Jiangxi, Peoples R China
[2] Nanchang Univ, Affiliated Hosp 1, Dept Pathol, Nanchang 330006, Jiangxi, Peoples R China
基金
中国国家自然科学基金;
关键词
miR-148a; pancreatic ductal adenocarcinomas; epithelial-mesenchymal transition; invasion; Wnt10b; Wnt/beta-catenin signaling; CLINICAL-SIGNIFICANCE; GASTRIC-CANCER; OVARIAN-CANCER; EXPRESSION; PROLIFERATION; MIGRATION; MIR-148A; ADENOCARCINOMA; METASTASIS; SURVIVAL;
D O I
10.3892/or.2017.5705
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Epithelial-mesenchymal transition (EMT) plays a critical role in the process of cancer invasion and metastasis. The Wnt/beta-catenin signaling pathway is known as a stimulative factor, which may trigger EMT and metastasis of cancer cells. In addition, several microRNAs (miRNAs) have been proven to regulate the EMT process. Recent research revealed that miR-148a is downregulated in pancreatic cancer. However, the definite role of miR-148a in EMT and invasion of pancreatic cancer is still unknown. The present study attempted to demonstrate the underlying mechanism of miR-148a in the regulation of EMT and invasion of pancreatic cancer cells. Our data revealed that the expression of miR-148a was markedly downregulated in human pancreatic ductal adenocarcinoma (PDAC) cell lines and tissues. In addition, the downregulation of miR-148a was associated with poor prognosis and EMT phenotype. Furthermore, restoration of miR-148a expression inhibited the EMT process, as well as the migration and invasion of BxPC-3 pancreatic cancer cells. Wnt10b, a promoting molecule of the Wnt/beta-catenin signaling pathway, was demonstrated by dual-luciferase reporter assay to be a direct target of miR-148a. Subsequently, we found that miR-148a negatively regulated the protein expression of beta-catenin, cyclin D1 and MMP-9, which were important components of the Wnt/beta-catenin signaling pathway. In conclusion, these findings revealed that miR-148a suppresses EMT and invasion of pancreatic cancer cells by targeting Wnt10b and inhibiting the Wnt/beta-catenin signaling pathway, and thus, miR-148a may serve as a novel therapeutic target for pancreatic cancer.
引用
收藏
页码:301 / 308
页数:8
相关论文
共 35 条
[1]   RETRACTED: Decrease expression and clinicopathological significance of miR-148a with poor survival in hepatocellular carcinoma tissues(Retracted article. See vol. 11, 2016) [J].
Ajdarkosh, Hossein ;
Dadpay, Masoomeh ;
Yahaghi, Emad ;
Pirzaman, Elham Rostami ;
Fayyaz, Amir Farshid ;
Darian, Ebrahim Khodaverdi ;
Mokarizadeh, Aram .
DIAGNOSTIC PATHOLOGY, 2015, 10
[2]   Silencing of miR-148a in cancer-associated fibroblasts results in WNT10B-mediated stimulation of tumor cell motility [J].
Aprelikova, O. ;
Palla, J. ;
Hibler, B. ;
Yu, X. ;
Greer, Y. E. ;
Yi, M. ;
Stephens, R. ;
Maxwell, G. L. ;
Jazaeri, A. ;
Risinger, J. I. ;
Rubin, J. S. ;
Niederhuber, J. .
ONCOGENE, 2013, 32 (27) :3246-3253
[3]   MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis [J].
Bloomston, Mark ;
Frankel, Wendy L. ;
Petrocca, Fabio ;
Volinia, Stefano ;
Alder, Hansjuerg ;
Hagan, John P. ;
Liu, Chang-Gong ;
Bhatt, Darshna ;
Taccioli, Cristian ;
Croce, Carlo M. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2007, 297 (17) :1901-1908
[4]   MicroRNA-Dependent Regulation of DNA Methyltransferase-1 and Tumor Suppressor Gene Expression by Interleukin-6 in Human Malignant Cholangiocytes [J].
Braconi, Chiara ;
Huang, Nianyuan ;
Patel, Tushar .
HEPATOLOGY, 2010, 51 (03) :881-890
[5]   Curcumin inhibits hypoxia-induced epithelial-mesenchymal transition in pancreatic cancer cells via suppression of the hedgehog signaling pathway [J].
Cao, Lei ;
Xiao, Xue ;
Lei, Jianjun ;
Duan, Wanxing ;
Ma, Qingyong ;
Li, Wei .
ONCOLOGY REPORTS, 2016, 35 (06) :3728-3734
[6]   Expression and the clinical significance of Wnt10a and Wnt10b in endometrial cancer are associated with the Wnt/β-catenin pathway [J].
Chen, Hongman ;
Wang, Yingmei ;
Xue, Fengxia .
ONCOLOGY REPORTS, 2013, 29 (02) :507-514
[7]   Hypoxia induces TWIST-activated epithelial-mesenchymal transition and proliferation of pancreatic cancer cells in vitro and in nude mice [J].
Chen, Shi ;
Chen, Jiang-zhi ;
Zhang, Jia-qiang ;
Chen, Hui-xin ;
Yan, Mao-lin ;
Huang, Long ;
Tian, Yi-feng ;
Chen, Yan-lin ;
Wang, Yao-dong .
CANCER LETTERS, 2016, 383 (01) :73-84
[8]   MiR-652 inhibits acidic microenvironment-induced epithelial-mesenchymal transition of pancreatic cancer cells by targeting ZEB1 [J].
Deng, Shichang ;
Li, Xiang ;
Niu, Yi ;
Zhu, Shuai ;
Jin, Yan ;
Deng, Shijiang ;
Chen, Jingyuan ;
Liu, Yang ;
He, Chi ;
Yin, Tao ;
Yang, Zhiyong ;
Tao, Jing ;
Xiong, Jiongxin ;
Wu, Heshui ;
Wang, Chunyou ;
Zhao, Gang .
ONCOTARGET, 2015, 6 (37) :39661-39675
[9]   MicroRNA-148a Suppresses the Proliferation and Migration of Pancreatic Cancer Cells by Down-regulating ErbB3 [J].
Feng, Hui ;
Wang, Yalei ;
Su, Jiaojiao ;
Liang, Hongwei ;
Zhang, Chen-Yu ;
Chen, Xi ;
Yao, Weiyan .
PANCREAS, 2016, 45 (09) :1263-1271
[10]   miR-15a inhibits cell proliferation and epithelial to mesenchymal transition in pancreatic ductal adenocarcinoma by down-regulating Bmi-1 expression [J].
Guo, Shixiang ;
Xu, Xuejun ;
Tang, Yichen ;
Zhang, Chaobin ;
Li, Jian ;
Ouyang, Yongsheng ;
Ju, Jingfang ;
Bie, Ping ;
Wang, Huaizhi .
CANCER LETTERS, 2014, 344 (01) :40-46